Term
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Definition
The cytoplasm and nucleus have molecular crowding. Results in a decrease in diffusion coefficients. Crowding increases macromolecular interactions by raising the chemical potential of a molecule. The phenomenon requires that large macromolecules need motors to move through crowded space AND b/c there is a smaller volume available, reaction is concentrated and increases productivity.
The likelihood of chemical interactions increases because they are close |
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Term
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Definition
| essentially is the cell bumping into thingstype of physical force cells may be exposed to among others such s shear, compression, tension, stretch, and gravity |
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Term
| non covalent bonds in biological macromolecules |
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Definition
1. Van der Waals
2. H-bonding
3. ionic
4. hydrophobic |
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Term
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Definition
weakest intermolecular force
need multiple for any strength
close/short range interactions
weak due to flux e- charges |
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Term
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Definition
entropy driven force hydrophobic regions self associate to exclude water from surface involves decreasing the disordering (delta S) of water molecules= entropy driven
ΔG=H-TΔS
adding a hydrophobic molecule in water creates more order :: (-) ΔS :: (+) ΔG = nonspontaneous |
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Term
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Definition
1. Ca storage
2. fatty acid synthesis
3. protein synthesis
4. glycosylation
5. drug metabolism |
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Term
| advantage of forming macromolecules from subunits |
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Definition
| can have a limited number of subunits whose sequences can be rearranged to give rise to many unique macromolecules |
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Term
| influences on cell appearance |
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Definition
| how the cells: 1. interact with environment 2. parts of the genome expressed 3. organization and make up all influence the size, shape, and function of a cell |
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Term
| advantage of compartmentalization in the cell |
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Definition
| 1. efficiency: decrease need for diffusion 2. regulation: eg. separating transcription form translation to make sure its correct sequence 3. safety: sequesters damaging processes from rest of cell |
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Term
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Definition
alpha C to alpha N
has resonance (partial (-)O on Carboxy and (+) N)
planar, trans, & rigid |
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Term
| Non-covalent association of prosthetic groups |
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Definition
1. metalloproteins: e- transfer rxns (eg. iron in ETC complexes)
2. hemoproteins: oxygen metabolism (Hb, Mb)
3. lipoproteins: transport F.A. and lipids
4. nucelotide-binding proteins: (G proteins) |
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Term
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Definition
| proteins with similar a.a seq and 3-D shape are considered part of same protein family. Often share a common domain but have different binding specifies and enzymatic activity. Classification is also based on functional characteristics |
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Term
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Definition
continuous stretches of amino acids that are folded into tertiary structures independently of the rest of the protein
composed of several motifs that come together |
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Term
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Definition
| domain or group of domains that carry our a particular function |
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Term
| Modifications of Amino Acid side chains |
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Definition
1. Carbohydrate Addition (glycosylation)--used for recognition. creates a "zip code" (irreversible)
2. Lipid Addition (helps protein interact with membrane--irreversible)
3. Regulation (phoshorylation, acetylation, ADP-ribosylation)
4. Modification of amino acid (oxidation, carboxylation) |
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Term
| eg. of enzymatic nucleic acids |
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Definition
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Term
| functional molecules involved in enzyme catalysis |
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Definition
1. amino acid side chains
2. coezymes: participate in activation transfer and ox-red rxn (NAD, FAD, TPP). Loosely attached to apoenzyme
3. metal ions acting as electrophiles (tightly bound to apoenzymes): used to transport electrons (eg. Fe in ETC Complex I & III)
without coenzymes, prostethic groups, and metal ions some enzymes are inactive (apoezymes). When attached they are active holoezymes ("WHOLE' enzymes) |
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Term
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Definition
speed of reaction that can be achieved when there is infinite amount of substrate available
Vmax=k3[Etotal] |
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Term
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Definition
| enzyme saturated with substrate even at low substrate concentrations & Vmax can be achieve at low substrate concentrations (has a high affinity for its substrate) |
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Term
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Definition
| the enzyme needs tons or high concentration of substrate in order to meet Vmax (has a low affinity for substrate) |
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Term
| enzyme turnover number (k3) |
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Definition
the # of substrates converted to product within a unit of time when enzymes are saturated (how fast is the enzyme in carrying out the process)
when not at saturation it is limited by the rate of diffusion |
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Term
| types of enzymatic specificities |
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Definition
1. absolute: enzyme catalyzes only one type of reaction
2. group: acts of one type of molecule (phosphate, methyl group, etc)
3. linkage: acts on a particular type of bond (eg. protease)
4. stereochemical: acts on type of steric or optical isomer |
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Term
|
Definition
loosely attached to enzymes.
involved in recognition of substrate and its movement into the active site (activates the substrate) |
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Term
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Definition
| v= (Vmax x [S]) / (Km + [S]) |
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Term
|
Definition
a group of enzymes that share a similar catalytic activity, but differ in sequence or some other property
my have differing specificity and regulation, tissue specific expression, kinetics
they can be from different genes or the products of the same gene by alliterative splicing |
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Term
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Definition
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Term
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Definition
bind at active site
decrease km, no change in vmax
overcome by increasing [S] |
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Term
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Definition
does not directly compete with substrate for binding site, but at some secondary site
lowers the concentration of active enzyme
decreases vmax, no change km
cannot be overcome with increased [S] |
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Term
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Definition
only binds to enzymes already bound to their substrate
decrease km, decrease vmax |
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Term
mechanism based inhibitors ("i didn't mean to")
irreversible |
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Definition
1. heavy metals: bind nonspecifically and may react with side chains and change normal enzyme activity
2. transition state analogs: look similar to transition state of substrate, bind and form TONS of non-covalent bonds with active site, thereby making it difficult to reverse. stuck in transition -looking state. Enzyme unable to proceed forward or backward in reaction
3. reactive inhibitors: substrate analogs. look like the substrates and form covalent bonds with the enzyme. Undergo irreversible reaction at the active site |
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Term
|
Definition
stabilize the active conformation of an enzyme
shifts cooperative enzymes equilibrium toward "relaxed state"
decrease km, no change in vmax
increases its affinity for substrate |
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Term
|
Definition
stabilize the inactive form of an enzyme
shifts cooperative enzyme equilibrium towards "tense state"
increase km alone
OR
increase km AND decrease vmax
decrease its affinity and the velocity of reaction |
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Term
|
Definition
type of allosteric regulation
binding of the substrate induces a conformational change in the subunit which then shifts mechanical energy to the other subunits--altering their binding affinity for the substrate
=shift in Relaxed/Tense state equilibrium
sigmoidal curve is indicative of cooperatively |
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Term
(6) ways to regulate enzymatic activity
(including protein-protein interactions) |
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Definition
1. sequestering/compartmentalization
2. Ezymatic activation (proteolysis of proezymes to zymogens)
3. covalent modifications
----
4. binding of regulatory proteins
5. release of regulatory subunit
6. formation of protein complexes |
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Term
| enzymatic regulation of pathways |
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Definition
1. opposing pathways often reciprocally regulated
2. at key control points (usually have different enzymes for opposing parts of pathway for key control)
3. at branch points between different pathways
4. often irreversible
5. feedback inhibition (often at first committed step or branch points)
6. feed forward activation (common in energy producing or toxin disposal, eg. urea or immune system inflammatory response) |
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Term
|
Definition
reduction of an aldehyde in an aldoese creates a polyol
all carbons have hydroxy groups |
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Term
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Definition
| repeating disaccharide structures |
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Term
| glycogen degrading enzymes |
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Definition
| glygocen phosphylase and debranching enzyme |
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Term
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Definition
accumulation of galactose because uable to convert galactose to galactose-1-phostate
lack enzymes for conversion to glucose-1-phosphate to enter glycolysis |
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Term
|
Definition
glucose--> glucose-6-phosate
(-) glucose-6-phosphate |
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Term
|
Definition
fructose-6-phospate--> fructose 1,6 bisphosphate
(+) fructose 2,6 bisphosphate, AMP
(-) citrate, ATP |
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Term
|
Definition
PEP--> pyruvate
(-) ATP
(+) fructose 1,6 bisphosphate |
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Term
| Pyruvate Dehydrogenase Complex |
|
Definition
activated by phosphatase (+) Ca
deactivated by kinase (+) acetyl coA, NADH, ATP
(-) pyruvate, ADP
PDC: (+) pyruvate, ADP, NAD, Ca
(-) acetyl coA, NADH |
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Term
| fatty acids transport into mitochondria |
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Definition
| fatty acyl coA transported by being converted to fatty aclycarnitine, then reconverted to fatty acyl coA when reaches mitochondria and can undergo beta-oxidation |
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Term
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Definition
fatty acid--> fatty acyl coA by fatty acyl coA synthase
activated by linking F.A. to AMP and coA |
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Term
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Definition
| cut fatty acyl coA by 2C to make acetyl coA 1, oxidation (FADH2) 2. hydration 3. oxidation (NADH) 4. cleavage |
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Term
| oxidation of ketone bodies |
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Definition
| acetate, beta-hydrozybutyrate and acetoacetate oxidized to make acetyl coA from ketone bodies produce NADH |
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Term
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Definition
1. ketone bodies
2. beta oxidation
3. pyruvate from glycoysis and PDC
4. amino acids
5. acetate |
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Term
|
Definition
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Term
| alpha-ketoglutarate dehydrogenase |
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Definition
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|
Term
|
Definition
|
|
Term
| alpha-ketoglutarate dehydrogenase |
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Definition
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|
Term
|
Definition
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Term
|
Definition
PEP--> OAA (gluconeogenesis)
(-) ADP
(+) acetyl coA
analogous to pyruvate kinase (glycolysis)
also important source of carbons for TCA |
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Term
| non-carbohydrate precursors |
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Definition
| alanine, glycerol, lactate (RBC, muscle) |
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Term
| sources of gluconeogenic amino acids |
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Definition
1. alpha ketogluterate
2. OAA
3. fumerate
4. succinyl coA
5. pyruvate |
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Term
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Definition
| bypasses first step of glycolysis to generate NADPH by oxidizing glucose-6-phosphate to ribulose-5-phosphate oxidative vs. non-oxidative pathway main enzyme: glucose-6-phosphate dehydrogenase, inhibited by high levels of NADPH |
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Term
| TCA cycle creases carbon backbones for pathways (4) |
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Definition
1. OAA and alpha-ketogluterate --> amino acids
2. maltate--> gluconeogenesis
3. succiyl coA--> heme
4. citrate--> fatty acid synthesis |
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Term
| fatty acid synthesis from citrate |
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Definition
1. excess citrate leaves mitochondria
2. citrate--> OAA+acteyl coA (citrate lyase)
3. acetyl coA--> malonyl coA (acetyl coA carboylase)
4. --->palmitate C16 (fatty acid synthase) |
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Term
|
Definition
turnover of a.a. is part of metabolism of proteins.
a.a. are deaminated to make C skeletons
transanimation method for removing nitrogen from a.a
released as ammonia and ammonium
glumatine and alanine (from muscle) major transporters
occurs mainly in liver and intestine |
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|
Term
PPP responds to need of cell
1. ribulose-5-P > NADPH
2. ribulose-5-p = NADPH
3. ribulose-5-P < NADPH
4. ribulose-5-P < NADPH AND ATP |
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Definition
1. SUPPRESS oxidative: use intermediates of glycolysis to make ribulose-5-P directly
2. ONLY oxidative, SUPPRESS non-oxidative
3. Oxidative AND Nonoxidative to regernate gylcosis intermediates
4. Oxidative and Nonoxidative to make glycolysis intermediates to go through glycolysis pathway |
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Term
|
Definition
1. PPP (glucose-6-phosphate dehydrogenase)
2. recycling of C back into TA after citrate has been transported out of matrix and broken down for F.A. synthesis
malate--> pyruvate (malic enzyme)
NADPH used for F.A. synthesis |
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Term
|
Definition
key enzymes: acetyl coA carboxylase (rate limiting step) fatty acid synthase
Steps
1. reduction
2. dehydration
3. reduction
4. cleaves
acetyl coA (ATP input)--> malonyl coA (immediate carbon donor)-->--> palmitate |
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Term
how does cell respond with FA/Beta-Oxidation with:
1. hi caloric diet
2. low caloric diet/starvation |
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Definition
hi calories: storage-- up regulation of fatty acid synthesis, esp acetyl coA carboxylase
low calorie: break down F.A. for energy--up regulation of Beta-oxidation |
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Term
|
Definition
acetyl coA + acetoacyl coA --> cholesterol
enzyme: HMG-A coA reductase
expends 2NADH, 4 ATP
used for production of hormones and for plasma membrane |
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Term
|
Definition
OAA--> PEP
(-) ADP
for gluconeogenesis
analogous to pyruvate kinase (glycolysis) |
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Term
| fructose 1,6-biphosphotase |
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Definition
fructose-1,6-BP--> fructose-6-P (gluconeogenesis)
(-) fructose-2,6-BP, AMP
(+) citrate
analogous to PFK-1 |
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Term
|
Definition
glucose-6-phosphate --> glucose (gluoneogensis)
analgous to hexokinase |
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Term
| non-essential amino acids |
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Definition
(11) naturally made in body, don't need to get from diet
(10) produced from intermediates of glycolis or TCA (alpha-keto, OAA, pyrtuvate-->alanine)
(1) TYR made by hydrolysis of PHE |
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|
Term
PLP-pyridoxal phosphate
CPS (carbonyl phosphate synthase)-- reg step
alpha-ketos
glutamate
orthinine
citruline
aspartate
urea
transanimation
ammonium
fumerate (connects Kreb to urea) |
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Definition
key terms of urea cycle
occurs in liver & intenstines |
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Term
|
Definition
acetyl coA--> maloynl coA
input of ATP
(-) palmitate
(+) citrate
rate-limiting step for f.a. synthesis
activated/deactivated by phosylation (like PDC) |
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Term
|
Definition
glycosidic enzyme in liver
high km, slower to import glucose bc more inovled with storage
(+) insulin
(-) glucagon |
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Term
|
Definition
makes glycogen
regulated by phos/dephosylated (insulin/glucagon) and glucose levels |
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Term
|
Definition
activated by insulin
makes F-2,6 BP which activates PFK-1 and makes cell proceed through glycosis |
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Term
|
Definition
1. increase glycogen breakdown
-glycogen synthase: inactive
-glycogen phosphylase and debranching: active
2. increase gluconeogenesis
-PFK-2: inactive
-glucose-6-phosphtase: active
-fructose-1,6,-BP: active
-pyruvate carboxylase: active
-PEP carboxykinase: active
3. increase beta-oxidation
4. decrease glycolysis
-hexokinase:inactive
-PFK-1: inactive |
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Term
|
Definition
1. increase glycogen synthesis
-glycogen synthase: active
-glycogen phosphtase & debranching: inactive
2. decrease gluconeogensis
-glucose-6-phostotase: inactive
-fructose-1,6-BPtase: inactive
3. increase fatty acid synthesis
-citrate lyase: active
-acetyl coA carboxylase: active
4. increase glyolysis
-hexokinase: active
-PFK-1: active |
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Term
|
Definition
frutose-6-P --> fructose 1,6 BP
(+) F26BP, ADP
(-) citrate, ATP
even in high levels of citrate, F26BP can overcome the inhibition citrate has on PFK-1 and allow glycolysis to occur, bc insulin is inducing PFK-2 to make F26BP which activates PFK-1..needs to respond to the hormone signals sent through the body |
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Term
| dependence of gluconeogensis on beta-oxidation |
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Definition
| can't do gluconeogenesis unless have the beta oxidation to produce ATP and NADH to drive gluconeogenic rxn |
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Term
MCADD
(medium chain acyl coA dehydrogenase deficiency) |
|
Definition
nonketogenic hypoglecemia
blockage of beta-oxid :: blockage of gluconeogenesis and ketone synthesis
=high levels of caritine in blood |
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Term
|
Definition
lacks mitochondria so undergoes anaerobic glycolysis
glycolysis -> pyruvate -> lactate
lactate can re-enter into liver for gluconeogensis, which creates glucose that can be transported to RBC
(cycle again)
=CORI CYCLE |
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Term
|
Definition
| RBC uses part of glycolysis (@ 1,3biphosphoglycerate) to make a regulatory molecule to maintain state of Hb |
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Term
| Energy Needs in Skeletal Muscle |
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Definition
muscles have a high need for energy but the capacity of the metabolic pathways cannot support them fast enough
creatine phosphokiase transfers a phosphate to creatine from ATP and energy harvested from the creatine phosphate made
creatine--> creatine phosphate (CPK)
other energy sources: blood glucose, fatty acids, ketone bodies, glycogen, amino acids |
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Term
| cardiac muscle energy sources |
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Definition
fatty acids
lactate (from RBC, skeletal muscle--muscle also use creatine)
glucose
need steady supply of oxygen |
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Term
| energy sources for brain/nervous system |
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Definition
brain always first gets glucose whenever available
also use:
lactate
acetate
pyruvate
keton bodies |
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Term
| energy sources for brain/nervous system |
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Definition
brain always first gets glucose whenever available
also use:
lactate
acetate
pyruvate
keton bodies |
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Term
| Phase Transitions & Lipid Bilayers |
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Definition
1. T > Tm = vicious--> fluid
2. shorter chain and more DB --> lower the Tm
3. more fluid
4. >Tm + sterols --> more viscous |
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Term
| displacement equation & D values for lipids and proteins |
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Definition
| x = 2 (Dt)^1/2 lipids D= 10^-8 to 10^-9 cm2/s (much slower) proteins D= 10^-11 to 10^-10 cm2/s (much faster) |
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Term
| membrane proteins mode of interaction with bilayer |
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Definition
1. transmembrane
2. membrane associated: by inner leaflet via amphiphatic alpha helix)
3. lipid linked
4. protein attached/peripheral |
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Term
| shorter fatty acids and cis (DB) |
|
Definition
decreases van der Waals interactions
:: keeps membrane fluid at low temperatures |
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Term
| paradoxical effect of cholesterol on membrane |
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Definition
at high temperatures, cholesterol will add rigidity
(near head groups)
at low temperatures makes it more fluid |
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Term
| Hinderance of Protein Lateral Diffusion |
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Definition
1. lattice membrane skeleton (actin and other proteins; can break, reform, and rearrange)
2. other proteins
3. extracellular matrix
4. diffusion barriers |
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Term
| membrane transport proteins |
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Definition
1. pump: use energy to pump molecules against electrochemical gradient
2. carrier: undergoes a conformational change to transport a molecule down its electrochemical gradient (uniport, symport, anitport)
3. Channel: transports molecules down electrochemical gradient (root of signaling for action potentials and secretory pathways) |
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Term
| genetic functions of proteins |
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Definition
1. transporters
2. enzymes
3. linkers
4. receptors |
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Term
|
Definition
made of glycerol backbone with fatty acyl chain
classes:
1. phosphoglycerolipids
2. phosphoshingolipids
3. glycolipids
4. sterols |
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Term
| protein membranes (general) |
|
Definition
1. transporters
2. create boundries
3. receptors
4. enzymes
5. adhesion |
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Term
|
Definition
signal recognition particle:
1. particle that binds to signal sequence on a growing peptide and halts its elongation
2. transports the peptide/ribosome complex to an SRP receptor
3. receptor guides peptide/ribosome/SRP complex to translocon in ER membrane
4. SRP and SRP receptor bind GTP for hydrolysis and dissociate and recycled for more rounds
...> peptide continues to grow through translocon into ER membrane until stop sequence
signal sequence is cleaved by signal peptide |
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Term
|
Definition
Sec61 heterotrimer
binds signal peptide
forms tight seal with ribosome to allow peptide to grow into ER membrane and continue elongation until stop sequence
translocon dissociates |
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Term
|
Definition
protease
on luminal surface of ER
cuts off signal sequence on b.s.p protein contranslationally |
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Term
|
Definition
spans membrane once
has 2 signal sequences (amino terminus, which is cleaved by signal peptidase and stop transfer signal, which is internal) |
|
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Term
| how to get opposite membrane dispostion |
|
Definition
| internal signal sequence =N terminus in lumen and C terminus outside ER membrane |
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Term
|
Definition
a dolichol is synthesized in the cytosol. once its lipid-linked oligosaccaride is made it is transported in the ER lumen. Once in the lumen it plays a part of the b.s.p to tag b.s.p porteins
dilichol transfers 3 Glc-9 Man-2 Glc Nac to the amino side chain of a protein containing Asp-X-Ser/Thr residue |
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|
Term
| movement of protein through biosynthetic secretory pathway |
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Definition
1. sorting motifs détermine what cargo is included
2. coat protein assembles and causes vesicle budding
3. vesicles move along microtubles tracks to target
4. specificity bind to target with aid of GTPases "switches" (eg. Sar1 in COPII and Rab in vesicular delivery) through tethering factors and SNARES
5. tethering factors on target recognize Rab on vesicle
6. T SNARES recognize and bind V SNARES= vesicle fusion |
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Term
|
Definition
eg. of budding and fusion through vesicular coat assembly
involved in transporting vesicles from ER to cis-Golgi
ER--> Golgi
1. Sar1 activated by exchange of GDP for GTP
2. Sar1 binds to membrane and recruits cargo
3. Sar1 also recruits Sec23/24 and tethering factors and others that drive budding
4. Sar1 GTPase results in loss of coat |
|
|
Term
| recycling of tethering factors and SNARES |
|
Definition
from cis-Golgi --> ER
budding factions with coat complex, COPI, and initiated by GTPase Arf1 |
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Term
|
Definition
eg. of retrograde movement and reclamation process
it is a sequence code on resident ER luminal proteins
used to like of like a dog tag saying that those proteins belong in the ER
when they escape ER into cis-Golgi, there are receptors in the cis-Golgi that recognize the KDEL sequence and salvage them back to ER lumen |
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Term
|
Definition
golgi is in constant state of flux
one sub compartment matures into the next as a result of retrograde movement va vesicle budding and fusion
cis (becomes cisternal)--> cisternal (becomes medial) --> medial (becomes trans)
new cis forms from ER vesicles |
|
|
Term
| sorting of lysosomal enzymes |
|
Definition
hydolases are enzymes bound for the lysosome
they bear a mannose-6-phosphate as their zip code
1. golgi makes modifications to the N-linked oligosacchride of the hydorlase
2. trans-golgi has a mannose-6-phospate receptor which acts as a cargo recruiter for the hydrolase
3. recruited into a bud coat activated by GTPase Arf, formed by AP-1 and clathrin
4. targeted for lysosome
5. Mannose-6-phospate receptor recycled back to trans Golgi |
|
|
Term
| constitutive secretory proteins (vesicle formation) |
|
Definition
products secreted in a dilute manner at a constant rate by exoctosis
carry plasma membrane proteins to cell surface
may be way to regenerate PM |
|
|
Term
| regulated secretory proteins (vesicle formation) |
|
Definition
stored and concentrated in granules
released as bolus in response to special stimulus or hormone (pauses for Ca signal)
granules undergo condensation and acidification to make them matured and concentrated |
|
|
Term
| Sorting of Proteins in Epithlial Cells |
|
Definition
Apical and basolateral side separated by tight junctions
Proteins must be delivered to specific site
apical: tend to get GPI anchored proteins delivered
basolateral: tend to get short-tyrosine containing sorting motifs
some some epithial cells, protein sorting takes place in basolateral endosome after initial delivery of both apical and basolateral proteins into that domain
Neuron as analog to Epithilial
axon domain: apical domain
somatodendritic domain: basolateral |
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Term
|
Definition
small GTPases involved in vesicle formation by recruiting tethering factors
activated when bound to GTP
recruit tethering factors and SNARES as well as other proteins such as clathrins, dynamins, adaptins to create vesicle coat |
|
|
Term
| Golgi Compartmentalization |
|
Definition
every protein has unique way of adding oligosacc
additions/trimmings take place in different parts of golgi
:: certain enzymes must be localized in different compartments of Golgi to carry out the processes of sugar modification on proteins |
|
|
Term
| General Endocytosis Pathway |
|
Definition
1. Ligand binds receptor
2. Clathrin and assesory proteins assemble
3. Coated pit pinches into cell to form vesicle
4. Vesicle uncoated
5. Vesicles form together to form a common compartment or early endosome
6. Sorting of early end some (receptors & ligands), acidification with H pump
6. receptors recycled or degraded
7. maturation into late endosome or to Golgi via transport vesicles |
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|
Term
|
Definition
eg. of ligand degraded and receptor recycled
1. Particle binds to receptor
2. go through endocytic process
3. receptor uncouples as early endosome begins to acidify (there are proton pumps)
4. receptor recycled while endosome continues to acidify and delivers to or becomes a lysosome
5. acid hydrolases cleave membrane and release cholesterol to move freely into membrane or wherever cell needs it |
|
|
Term
| Tranferrin & Iron endocytosis |
|
Definition
e.g.. of both ligand and receptor recycled
1. Iron and molecule binds to receptor
2. Taken in by endocytosis
3. Forms vesicle and becomes endosome
4. Hydrogen pump converts early endosome to a late endosome
5. As lysocosme acidifices, iron comes off
6. Activates a signal that decoats and releases receptor and apotransferrin back to surface–
7. The higher pH at cell surface causes release of apoptranferin—now free to bind iron again and restart process
apotranferrin binds iron--> becomes transferrin
transferrin able to bind receptor
Endocytosis process
Fe taken and processed for cell use
apotranferrin and receptor recycled back to cell surface |
|
|
Term
|
Definition
eg. of both receptor and ligand degraded
1. EGF binds to EGF receptor
-Binding itself causes a signal: activation of kinase to begin signal cascade
2. Formation of coated vesicle
3. When body wants to stop signal it puts receptor EGF and its receptor in a lysosome and degrades them.
Fc receptor is another example |
|
|
Term
| IgA receptor in endocytosis |
|
Definition
eg. of ligand and receptor transported
1. IgA accumlates at cell surface
2. carried into cell and exocytosed into bile
3. receptor cleaved |
|
|
Term
| Infectious Agents and Toxins using Endocytosis Pathway |
|
Definition
1. some bacteria and parasites use endosomes of site of replication by circumventing endosomes fusion lysosomes
2. toxins insert membrane at low pH and gain access to cytoplasm through the acidic endosomal compartments
3. viruses take up into cell by endosomes and their fusogenic activity is activated by acidification process and then able enter cytoplasm |
|
|
Term
|
Definition
| type of Type I transmembrane protein that have an additional protease cleavage on luminal side of stop sequence and additional attachment of glycolipid |
|
|
Term
| fluid phase uptake vs. receptor mediated uptake |
|
Definition
fluid phase: random intake of ligands is inefficient. it is a clathrin independent process
receptor-medialted: efficient uptake of selected substances by specific surface receptors. utilize clathrin-coated membrane pits |
|
|
Term
| phagocytosis vs. pinocytosis |
|
Definition
phagocytosis: specialized case of endocycitic activity. Can be receptor mediated
pinocytosis: constitutive property of all cells. subdivided into fluid phase or receptor mediated uptake |
|
|
Term
| (4) Uptake Pathways/Functions of Lysosomes |
|
Definition
1. Endocytosis: lysosome--> late endosome via carrier vessicles
2. Phagocytosis: specialized endocytosis
3. Autography: engulfment of intracellular membranes and organelles
4. Crinography: Direct delivery from cytosol (direct fusion of secretory granules with lysosomes) |
|
|
Term
|
Definition
hydrolyses are glycoproteins
1. mannose-6-phosate marker is added to hydrolase in the cis-Golgi in a 2 step process by N-acetylglucoamine phosphate and N-aceylglucoamine phosphoglycosidase
2. Tag prevents further processing in the Golgi
3. mannose-6-phosphate receptor in the trans-Golgi recognizes the hydrolase as lysosome enzyme and signals the formation of a vesicle
4. low pH of the vesicle causes the enzymes to be released from receptor, which then cycle back to trans-Golgi for reuse
5. hydrolase delivered to lysosomes and phosphate is removed to prevent the recycling of the hydrolase |
|
|
Term
| lysosomal membrane proteins |
|
Definition
use an alternative route following synthesis and processing through Golgi.
At the trans-Golgi the proteins are targeted to the PM and then endocytosed |
|
|
Term
|
Definition
| lysosomal disease with mutation in N-acetylglucosamine transferase Deficiency in lysosomes - accumulate GAGs (glycosaminoglycans). Caused by lack of M6P marker on proteins that should go to the lysosome |
|
|
Term
|
Definition
defect in alpha-L-iduronidase
lysosomal disease in which GAGs build up. (hydrolase mutation)
Disease allowed discovery of SCAVENGER PATHWAY - cells with mutant hydrolases intake exocytosed non-mutant hydrolases from other cells |
|
|
Term
|
Definition
lysosomal disease with mutation in Beta-N-acetylhexosaminidase (GM2-gangliosidase)
Gangliosides not broken down, large accumulations of GM2 |
|
|
Term
|
Definition
| lysosomal disease with mutation with glucosylceramide Beta-glucosidase |
|
|
Term
|
Definition
| lysosomal disease with mutation in sphingosyelinase |
|
|
Term
|
Definition
beta oxidation of fatty acids
detoxification with amino acid oxidases
use O2 to remove H2 atoms from molecules to make H2O2 which is used by catalase to oxidize substances |
|
|
Term
|
Definition
enzyme in peroxisomes that degrades the peroxide
makes up 40% of the peroxisomal protein |
|
|
Term
|
Definition
perxisome proteins are made by cytoplasmic polyribosomes aka polysomes (not part of BSP)
incorporated into peroxisome by carboxy terminal targeting sequences (PTS1 & PTS2, types of SKL) and transporters
peroxisomes can cane be increased by proliferators (eg. clofibrate)
new peroxisomes generated by fission |
|
|
Term
| Peroxisome Biogenesis Disorder (PBD) |
|
Definition
autosomal recessive
result from defect in the import of peroxisomal proteins= peroxisomal ghosts |
|
|
Term
|
Definition
mutation in transport of peroxisome enzymes
absence of peroxisome catalase
result from mutation in PMP70, an ATP Binding Cassette (ABC) that is involved in transport of peroxisomal enzymes |
|
|
Term
| X-linked adrenoleukodystrophy |
|
Definition
| peroxisome mutation defect of VLCFA (very long chain fatty acids) due to lack of VLCFA CoA synthetase activity =demyelination and adrenal insufficiency and death |
|
|
Term
|
Definition
| protein that initiates the formation of a vesicle with cargo |
|
|
Term
|
Definition
Dynamin: protein that helps vescile pinch off
=vesicle formation |
|
|
Term
|
Definition
disease of endocytosis of LDL
LDL lacks cytoplasmic tail and can't bind adaptin
=LDL can't be internalized |
|
|
Term
|
Definition
glycoproteins that are enzymes in the lysozome
function to degrade things
although pH of lysosome is low, hydrolyses are not degraded/denatured because they are tightly folded in acidic conformations
These hydrolases sometimes leak into cell, but in the higher pH environment they are not active and therefore not dangerous to the cell |
|
|
Term
|
Definition
lysosome transcription factors
most lysosomes are regulated by the same TF, the genes for lysosomes have homologous DNA sequences in their promoters
if the body has a high need for lysosomes, the TFEB is translocated to the nucleus to induce the transcription of DNA to make more lysosomes |
|
|
Term
|
Definition
signals sequences on the carboxy terminal of proteins targeted for peroxisomes
most common type of SKL |
|
|
Term
|
Definition
complex which binds to the peroxisomal enzymes as they are being synthesized on polyribosomes
help with targeting to peroxisome or through membrane |
|
|
Term
|
Definition
heterotrimeric G proteins
Gs
Gi
Golf
Ggust |
|
|
Term
|
Definition
|
|
Term
| other G proteins (not large or small) |
|
Definition
|
|
Term
|
Definition
1. GDP/GTP cycle
-active when bound to GTP
-inactive when bound to GDP
2. GTP exchange factors: promote
eg. GEF, GDI (vs. GAP which does not promote)
3. GTPases: hydrolyze terminal phosphate group
eg. GAP |
|
|
Term
|
Definition
1. timers
2. switches
3. special functions: elongation, membrane scission |
|
|
Term
|
Definition
| heterotrimeric (3 different subunits): alpha, beta, gamma |
|
|
Term
|
Definition
stimulates adenylate cyclase
its stimuluses are beta-adrenegic, glucagon, PTH |
|
|
Term
|
Definition
inhibits adenylate cyclase
stimulus: acetylcholine, alpha-adrenrgic |
|
|
Term
|
Definition
effects tyrosine kinases
stimulus is thrombin |
|
|
Term
|
Definition
a small G protein relays switch to activate pathways regulated by GDP/GTP cycle
Reacts indirectly through adaptor molecules and activates affecter pathways common mutation in cancer
Ras undergoes acylation to localize to membrane by farnesyl transferase |
|
|
Term
|
Definition
G protein
used for vesicle trafficking |
|
|
Term
| G proteins involved in cytoskeleton reorganization |
|
Definition
Rac Rho Cdc42
(cytoskeleton able to migrate and move through changes in cytoskeleton)
|
|
|
Term
| modes of intercellular communication |
|
Definition
1. endocrine
2. paracrine/autocrine
3. juxtacrine |
|
|
Term
| modes of intermolecular communication1 |
|
Definition
1. secondary messangers (eg. cAMP)
2. direct contact
3. phosphoylation
-addition of phosphate to see/thr/ty
-When this energy consuming process occurs, protein often changes conformation and activity or promote portein-protein interactions.
-Dephosylation may turn off or turn on signaling. P---Proteins interacting with each other may require phosylation or use another way for biochemical interaction |
|
|
Term
|
Definition
proteins can be regulated/switched between off and on by phosphylation by kinase or dephosylation by phosphatase or by GTP/GDP cycling
=regulation of signaling |
|
|
Term
| nuclear/intracellular receptors |
|
Definition
hydrophobic signal molecule passes through membrane and binds to intraceullar receptor.
induces a conformational change and allows receptor to enter nucleus and bind to regulatory unit of DNA to induce gene expression |
|
|
Term
| Types of Membrane/Extracellular Receptor |
|
Definition
1. ion channel linked receptor
2. G protein linked receptor
3. enzyme linked receptor |
|
|
Term
| ion channel linked receptor |
|
Definition
when receptor is unbound to ligand, it excludes ions from passing through membrane
when signal molecule binds, receptor has conformational change and allows ions to flow through the membrane |
|
|
Term
|
Definition
in the absence of signal molecule, the receptor dimer is separated and inactivated catalytic domain
when signal binds, the receptor parts come together to form a dimer with an activated catalytic activity
eg. Hematotreopic/Cytokine Growth Factor Receptor with JAK tyrosine kinase (recruited bc receptor doesn't have intrinsic kinase activity) |
|
|
Term
| G protein linked receptor |
|
Definition
7 transmembrane receptor, G protein, and enzyme are all separate and inactive in the absence of signal
ligand binds to 7 transmembrane receptor and G protein comes over to it and also gets activated
Beta-gamma subunit of G protein detaches and goes to the enzyme to activates it |
|
|
Term
| Cytokine/Hematopoietic Growth Factor Receptors |
|
Definition
example of an enzyme linked receptor w/o intrinsic kinase activity
cytokine receptor has dimer that is separated in the absence of cytokine
1. when cytokine binds the two parts of receptor forms a dimer
2. receptor recruits JAK tryosine kinases which activate the signal by phosphorylating one another and the receptor
3. STAT gene regulatory protein forms and goes to nucleus
4. STAT combines with other regulatory proteins at the regulatory domain of the DNA and induces transcription of |
|
|
Term
|
Definition
| small G protein aids in vesicle transport to target hydrolyses from the trans-Golgi to lysosomes also involved in retrograde vesicle transport to return ER lumen proteins back from cis--> ER with KDEL sequence |
|
|
Term
|
Definition
| involved in vesicle formation with COPII cargo movement from ER--> cis Golgi |
|
|
Term
|
Definition
7 transmembrane, G protein (GDP bound), and enzyme all separate
1. signal molecule binds to receptor and causes alpha subunit of G protein to bind to recepetor
2. G protein exchanges GDP for GTP on alpha subunit to activate it
3. beta-gamma subunit separates from the alpha subunit
4. G protein goes on to transduce signal |
|
|
Term
|
Definition
a G proteins identity is determined by specific genes
have 3 subunits (alpha, beta, gamma)
alpha subunit: binds to the receptor. has the ability to bind to a variety of receptors=promoscuity in recognition
involved in signal recognition, transduction, and amplification |
|
|
Term
| PKA signal amplification pathway |
|
Definition
1. ligand binds to heterotrimeric receptors 2. G protein binds and undergoes its GTPase actvity to trade GDP for GTP, thereby activating it 3. Beta-gamma subunit goes to adenylate cyclase and activates it 4. activation of adenylyl cyclase causes ATP to be hydrolyzed to cyclic AMP (cAMP) 5. cAMP activates PKA 6. PKA enters nucleus and phosylates a transcription factor to induce transcription of DNA
[image] |
|
|
Term
| PKC signal transduction pathway |
|
Definition
1. ligand binds to heterotrimeric receptor 2. G protein binds and undergoes GTPase activity 3. G protein beta-gamma subunit activates phospholipase 4. phospholipase dissociates diacylglycerol from inositol triphospate 5. inositol triphosphate opens ER Ca ion channels 6. released Ca binds and diacylglycerol to PKC and activates it to further transduce signal
[image] |
|
|
Term
|
Definition
Gs (stimulates adenylate cyclase stays on
:: G protein unable to hydrolyze GTP into GDP to deactivate the signal transducer
=continued activation of adenylate cyclase and increasingly high levels of cAMP
this causes decreased Na absorption and increased Cl secession
=rice stool |
|
|
Term
|
Definition
Gi (inhibitor of adenylate cyclase) is degraded
=cAMP build up |
|
|
Term
| GDP/GTP cycling and GEF/GAP |
|
Definition
|
|
Term
|
Definition
| example of enzyme linked receptor
[image] |
|
|
Term
|
Definition
located in plasma membrane
important in signal transduction
has wide diversity of ligands
has tyr kinase domain
have structural variability but structure conserved on cytoplasmic side |
|
|
Term
|
Definition
SH2: recognizes phosphotryrosine proteins and the C terminal Tyr527—when that is phosylated it binds to SH2
also has proline rich domain
Src contorlled by being in off configuration and regulated by 2 events:
Interaction of SH3 domain with proline rich domain
SH2 domain with phosytryrosine
When phostyrosine is mutated, and phosylated src gene always on
SH3: sticks with proline rich region |
|
|
Term
| nonreceptor tyrosine kinase |
|
Definition
JAK
Abl
Src
act kind of like adaptor proteins on cytoplasmic side of cell to conduct signals |
|
|
Term
|
Definition
| protein which acts as a mothership and allow other proteins to dock. (eg. IRS: Insulin Related substrate) |
|
|
Term
|
Definition
important for protein-protein interaction.
Bridges two proteins = complex of 3
= facilate signal transduction pathways
nonreceptor tyrosine kinases (JAK, Abl, Src) |
|
|
Term
|
Definition
Src virus inserts bad info into cell
products encoded is src onogene
Differs with our normal src b/c viral one is missing last 40 a.a. which encode for the tyrosinekinas
=always on and unable to be regulated
--> cancer |
|
|
Term
| signal transduction theraputics |
|
Definition
|
|
Term
|
Definition
translocation between chromosome 9 and 22
causing production of bcd-abl gene
bcr-abl gene which has tyrosine activity
Bcr-Abl is a potent tyrosine kinase—is a kinase and a docking site for many signal transduction proteins= short cirucuts RBC development= big spleen, high platelet blood count, then goes to crisis phase and have blasts in the body
=chronic myeloid leukemia
can be treated with imatinib and dasatinib which block bcr-abl by targeting the growth factor receptor |
|
|
Term
|
Definition
hypothesized that mitochondria developed from eukaroyote cell taking up a aerobic prokoyrate cell
=may explain why mitochondria isn't part of b.s.p. and instead takes up proteins from cytosolic ribosomes |
|
|
Term
|
Definition
soluble space
outlined by cristane to increase surface area
site of beta oxidation, pyruvate oxidation, TCA
contains many copies of mitochondria DNA, special mito ribosomes, tRNA, and enzymes needed for expression of mito genes |
|
|
Term
| Mitochondria Outer Membrane |
|
Definition
| very permeable because of large channel forming pro tine (porin) |
|
|
Term
| Mitochondria Inner Membrane |
|
Definition
folded into cristae to increase surface area
has proteins for 3 functions
1. ETC
2. ATP syntahse
2. Transport proteins
allows passage of metabolites in/out of matrix
very selective--imperable to ions and most small charged molecules
H+ gradient established across this membrane to drive ATP synthase |
|
|
Term
| Mitochondria Intermembrane Space |
|
Definition
| site where H+ are pumped into for electrochemical gradient |
|
|
Term
| Highly oxidative tissue & mitochondria |
|
Definition
Highly oxidadive tissue have a lot of mitochondria (muscle, cardiac muscle, kidney, etc)
Lot of energy requirements |
|
|
Term
|
Definition
undergo fission/fusion reactions
new mitochondria are created by adding substances to existing mitochondria and uneven distribution of components |
|
|
Term
|
Definition
only encodes 13 proteins (including ATP synthase and complexes of ETC)
encodes for 2 ribsomoal genes (rRNA) and 22 tRNA's
makes polygentic transcripts that are cleaved later
no introns most mRNA ends in U and polymerase just adds on AA for termination
=efficient use of space on mtDNA
Ribosomal at one end of molecule and next to D-loop region—all modification occurs here (has promoters for bidirectional replication and origin of replication)
no other regulatory sites in mitocondria DNA |
|
|
Term
| mitochondria dependence on nuclear genes |
|
Definition
nuclear genes account for most of mitochondria's function and structure
mitochondria needs about 1000 proteins, 100 needed for oxidation, 13/100 come from the mitochondria
=all others from nuclear genome
regulatory factors and polymerases come from nucleus
=mitochondria can make proteins but does not have the ability to regulate itself or control synthesis bc most controlled by nuclear genes and have to be localized to the correct sub compartment in mitochondria |
|
|
Term
|
Definition
ribosomes are bacteria like and affected by antibiotics
have an inhibitory effect on mitochondria but doesn't
kill them because mitochondria has a slow turnover rate |
|
|
Term
| protein targeting from nucleus to mitochondria |
|
Definition
proteins have signal peptides (recognized by receptor in outer membrane) that direct it to the mitochondria
signal peptide is (+) hydrophobic reside and amphipatic alpha helix
-it is not a signal that targets, but the amphiphatic structure
-targeting signal removed by signal peptidase
input of the protein into the mitochondria is post-translational
translocation of proteins into the mitochondria requires the hydrolysis of ATP
1. insertion into cytoplasm (does not require energy), but just loosely associated
2. hydrolysis of ATP= protein able to be translocated into mitochondria |
|
|
Term
|
Definition
involved in protein import into mitochondria
has receptor component and translocation channel
allows entrance of proteins into the inter membrane space, then imported into inner membrane by appropriate receptor |
|
|
Term
|
Definition
transports proteins from inter membrane space to the inner membrane
it is the least specialized of inner membrane transporters |
|
|
Term
|
Definition
| imports membrane spanning proteins from the inter membrane to the inner membrane space (so usually proteins involved in ETC) |
|
|
Term
|
Definition
| protein that transports proteins from the matrix into the inter membrane space |
|
|
Term
|
Definition
chaperones utilized both cytoplasmically and intercelluarlly to maintain shape of unfolded protein while its being translocated from cytosol into mitochondria uses ATP
ATP hyrolysis can be as a result of hsp dissociating from entering protein or conformational change/tugging movement
[image] |
|
|
Term
|
Definition
Protein goes through membrane by grinding in, when it gets into matrix side, chaperone (hsp70) binds sequentially and causes it to moves it through matrix dissociation of hsp70 is ATP dependent
|
|
|
Term
| Cross Bridge Ratchet Model |
|
Definition
protein translocated into membrane by binding of hsp70 but the ATP requirement comes from the conformation change hsp70 makes to pull the protein into membrane
|
|
|
Term
| 2 methods proteins can get into inner membrane space |
|
Definition
| 1. TOM--> OXA
2. just inner membrane translocator
[image] |
|
|
Term
| Mitochondria Genetic Code |
|
Definition
has slightly different coding
=genes are unable to be therapeutically introduced into the mitochondria
=hard to cure mitochondria diseases |
|
|
Term
|
Definition
mt DNA forms a triple stranded strux that forms shape of D
has 2 promoters, Pl (light) and Ph (heavy), go in different directions
Transcription is bidirectional from the D-loop to make Hstrand and Lstrand |
|
|
Term
| mitochdondria DNA replication and transcription |
|
Definition
transcription is coupled with replication
replication is bidirectional and semi-conservative
1. transcription begins at light strand promoter (with help of TF and mt RNA polyermase)
2. RNAase (endocluease) cleaves the transcript to create a primer template for the origin of replication for the heavy strand
3. Heavy strand replicates, when it reaches the origin of replication for light strand, initiates replication of light strand in the opposite direction
[image] |
|
|
Term
| Glycerol-3-phosphate shuttle |
|
Definition
way to get NADH from cytosol to matrix for ETC loss of energy because convert NADH to FADH2 used when need quick spurt of energy and willing to take energy loss (ex. in sperm)
makes 8 less ATP than malate-aspartate shuttle
[image] |
|
|
Term
|
Definition
makes 8 more ATP than Glycerol-3-phosphate shuttle
[image] |
|
|
Term
| H+ gradient makes pH and voltage gradient |
|
Definition
|
|
Term
| pyruvate/Pi import and ADP/ATP exchange |
|
Definition
| exiting of ATP is (-4) and ADP import is (-3) via ADP/ATP translocase
= changing proton gradient by value of 1
=voltage gradient drives the ADP-ATP exchange
when importing pyruvate, it has a negative charge and comes in with phosphate (+ )= charge neutral, therefore eliminating a charge on the outside
=charge neutral but effect H concentration= kind of energy expensive because disrupts the gradient
voltage gradient drives ATP export
pH gradient drives pyruvate import
[image] |
|
|
Term
|
Definition
ATP synthesis driven by downhill flow of H+ through Fo subunit induces conformational change on the F1 and causes ATP to be formed and released
need both proton gradient and ATP synthase to generate ATP
[image] |
|
|
Term
| Reversible Action of ATP Synthase |
|
Definition
|
|
Term
|
Definition
ΔG' =-nFΔE'
n=# of electrons
the oxidation of NADH is (-)ΔG while the synthesis of ATp is a (+)ΔG, therefore oxidation of NADH drives the synthesis of ATP= basis of ETC
strong reducing agents like NADH have a (-) redox potential (E') and are at the beginning of the chain
strong oxidation agents like O2 have a (+) redox and are the final eletron acceptors
|
|
|
Term
|
Definition
| located on cytochrome C, coenzyme Q, Complex 3 and 4 alters the redox potential of the molecule its attached to cytochrome c, Complex 3 & 4 |
|
|
Term
|
Definition
aka NADH dehydrogenase or NADH-Q reductase
4 protons pumped per electron pair
iron/sulfur center
accepts 2 e- from NADH and gives to Q
mutation=LHON (middle aged blindness) |
|
|
Term
|
Definition
aka cytochrome reductase
4 protons pumped per electron pair
2 heme, 1 sulfur/iron center |
|
|
Term
|
Definition
aka cytochrome oxidase
2 protons pumped per electron pair
2 heme, 2 copper/iron center |
|
|
Term
| molecules which block e- transfer |
|
Definition
|
|
Term
| sources of FADH2 for entering ETC |
|
Definition
| glycerol, fatty acyl coA, and succinate dehydrogenase (in TCA) |
|
|
Term
|
Definition
lipid soluable carrier
heme, iron, sulfur, ubiquinone
site of superoxide formation
sometimes can transport electron 1 at a time to molecular oxygen creating reactive oxygen species
=mitochondria theory of aging that makes degenerative tissue |
|
|
Term
|
Definition
hydrophobic molecule
able to go through inter membrane space
heme iron changes from ferric (FeIII) to ferrous (FeII) state whenever it accepts an electron.
Ferric = oxidized; ferrous = reduced
Hydrophobic character of heme environment makes reduction potential of cytochrome c more positive than that of heme in aqueous solution
also part of apoptosis (intrinsic) |
|
|
Term
|
Definition
| 10 total protons shuttled per electron pair
synthesis of ATP made by flow of 3 H+ through ATP Synthase
[image] |
|
|
Term
|
Definition
|
|
Term
|
Definition
H+ gradient uncoupler
lipid soluble weak acids act as H+ carriers
dissipate H+ gradient by providing alternative to ATP
synthase
short circuit dissipates proton motive force
the cell reacts by increasing e- transport in presence of the uncoupler, in an attempt to maintain proton gradient
the rate of e- transport controlled by ATP/ADP ratio |
|
|
Term
|
Definition
H+ gradient uncoupler in brown fat
resembles ATP/ADP translocase and allows H+ flow
down the gradient without ATP synthesis
heat produced instead
the cell reacts by increasing e- transport in presence of the uncoupler, in an attempt to maintain proton gradient
the rate of e- transport controlled by ATP/ADP ratio |
|
|
Term
|
Definition
The two can be distinguished by
1. cytoplasmic acidification (apoptosis)
2. externalization of phosphatidylserine (signal released in apoptosis cells to be engulfed)
3. fragmentation of genomic DNA aka DNA laddering
4. Mitochondrial injury
5. proteolysis of intracellular proteins |
|
|
Term
| morphological changes of apoptosis cell |
|
Definition
1. shrinking cytoplasm
2. condensation of chromatin
3. membrane blebbing
4. engulfment of dying cells by neighboring cells
5. degradation of DNA (one of first signs) |
|
|
Term
| morphological changes of necrosis |
|
Definition
cell and organelle swelling
=cell lysis and inflammation |
|
|
Term
|
Definition
1. decrease of cytoplasm pH (acidification
2. production of reactive oxygen species (ROS) that is made by mitochondria
3. phosphatidylserine is externalized when cell receives a cell death signal and causes neighboring cells to engulf it
4. DNA is degraded, one of first signs of apoptosis
5. specific proteolysis of proteins in the cell that allow it to be dismantled and for cell death to occur |
|
|
Term
|
Definition
as cell dies during apoptosis, the DNA is fragmented into this laddering pattern
because DNA is wrapped around proteins so get fragmentation bc the DNAase cuts at DNA wrapped around histones
=not random sheering but controlled process |
|
|
Term
| apoptosis and organism development |
|
Definition
apoptosis is a paradoxical event bc it needs to occur in order for organism to survive
During development there are cells that play key role, but later some of those cells are no longer necessary later on in development
if remove genes that play a role in apoptosis, you can have development dysfunction
eg. resorption of tadpole tails, menses, etc. |
|
|
Term
|
Definition
aka "kiss of death"
recognize virally infected cells or tumor cells and destroy them
interacts with infected cell and assists its suicide by releasing protein that activates endogenous suicide program in the cell |
|
|
Term
|
Definition
aka "guardian of the genome"
deletes cells with irreparable DNA damage
cancer cells often mutate this gene and are able to overcome cell death and grow massively |
|
|
Term
| unregulated apoptosis disease: excess death |
|
Definition
Neurognerative diseases
-Alzhemier's
-Huningtons
-ALS
Ischemia
-Stroke
-MI
=increased caspase activity |
|
|
Term
| unregulated apoptosis disease: deficient death |
|
Definition
cancer
autoimmune: lupus, thyroid disease, diabetes
=inhibited/decreased caspase activity |
|
|
Term
|
Definition
Bax
Bak
BID
Aparf-1: activates caspase-9
Ced 3-killer gene in C. elegans
Egl 1- activates killer genes in C. elegans |
|
|
Term
|
Definition
Bcl-2
Bcl-xl
Ced 4-- kills killer genes
Ced 9- survival gene in C. elegans (inhibits activators of killer genes, eg. Egl-1) |
|
|
Term
|
Definition
cysteine proteases with aspartate substrate selectivity
cut proteins with asp residues: Asp-X
~12 human caspases that differ in substrate recognition sequence (have some variation of Asp)
eg. Casp 3, 7, 6
related to Ced-3 cell death gene
made as proenzymes that are activated by cascade of proteolysis
promising for drug targets |
|
|
Term
| proteolytic cascade to activate caspases |
|
Definition
They are made as proezymes (inactive until they are activated by cleavage)
Have to be processed by other capsases to be activated
2 of herterdimers come together to make active caspase which is a tetramer |
|
|
Term
| Intrinsic/Mitochondria Apoptotic Pathway |
|
Definition
occurs inside the cell
apoptosis is activated by stimuli (non TNF family molecules)
cytochrome c is encouraged to be released from mitochondria
release of cyt c is regulated by the binding of pro-apoptotic (Bax, Bak, Bid) and anti-apoptotic enzymes ( Bcl-2)
--who wins the fight depends which side of family brings more people to activate/inhibit release of cyt c
if cyt c is released, activates Aparf-1 which recruits several procaspases-9 that cluster together and begin to cleave each other= caspase cascade |
|
|
Term
|
Definition
| complex of cytochrome c, Apaf-1, procaspase 9 |
|
|
Term
| Extrinsic Apoptotic Pathway |
|
Definition
1. cytokines eg. TRAIL (TNF family) bind to receptor
2. receptor timerizes on cytoplasmic side = death domain formed
3. FADD (adaptor protein) is recruited and exposes the death domain
4. Procaspase8/10 are recruited to the complex
5. the clustering of the caspases causes a change in the thermodynamics and induces them to cleave one another=cascade of capsases= cell death |
|
|
Term
|
Definition
way that procaspases are activated
the forced clustering or procaspases starts proteoltyic event
once one caspase is activated, a cascade of proteolysis occurs= caspase cascade=amplification of death signal |
|
|
Term
| Regulation of Intrinsic Apoptosis |
|
Definition
Bcl-2: anti-apoptotic gene. prevents release of cytochrome c
heat shock proteins: hsp 70, hsp 90 inhibit apoptosome assembly |
|
|
Term
|
Definition
Regulation of Extrinsic Apoptosis
dominant negative caspase 8 (anti-apoptotic)
Looks like Caspase 8 but doesn’t have active asp protelytic site with molecular blade Binds to death receptor and hence prevents procaspase 8/10 from being recruited and activated |
|
|
Term
| IAP (Inhibitors of Apoptosis) |
|
Definition
a family of anti-apoptotic proteins
eg. XIAP and survivin
inhibitors of downstream caspases |
|
|
Term
| How the caspases actually kill the cell |
|
Definition
1. inhibiting anti-apoptotic proteins by cleaving them
(eg. Bcl-2 and dismantle cytoskeleton)
2. activate dormant pro-apopotic proteins (caspases, Bax, Bak, BID, and kinases) |
|
|
Term
|
Definition
excessive cell growth and NO cell death
=loss of pro-apoptotic genes/Killers (Bax, BID, Bak, caspases, kinases)
AND
=over activation of anti-apoptotic genes (Bcl-2, FLIP, survivin) |
|
|
Term
| Things that determine the permeability of a substance |
|
Definition
1. temperature
2. solubility
3. molecular size
membrane is permeable to small hydrophobic molecules (O2 and CO2) and small uncharged molecules (ethanol) |
|
|
Term
|
Definition
ratio of the concentration of a compound in two phases of a mixture of immesible compounds in equilibrium
a measure of differential solubility of the compound between two solvents |
|
|
Term
|
Definition
aka shuttles or exchangers
transport molecules across the membrane by facilitated diffusion
selectively binds a ligand/molecule on extracellular side, which induces a conformational change and allows the molecule to be transported across the membrane
moves things down their concentration gradient
movement is slow
Subsets: antiports, symports, uniports |
|
|
Term
|
Definition
transport ions down their concentration gradient
opening of the channel can be induced by a voltage (eg. Na/K channel) or binding of a ligand (ionotropic vs. metabotropic)
no energy requirements |
|
|
Term
| ionotropic gated channels |
|
Definition
receptor channels ligand binding site is actually part of the channel the act of ligand binding causes a conformational change on the ligand and induces it to open/close and move ions through the membrane
faster than metabotropic
e.g. of channel families: Gluamate, GABAa (inhibitory transmitter in brain), glycine (Cl transporter in spinal cord), Acetylcholine (nicotinic receptor in muscle)
[image] |
|
|
Term
| metabotropic gated channels |
|
Definition
receptor that are indirectly linked to a ion channel via the transduction of a signal by a G protein much slower than ionotorpic eg. of channel families: GABAb, acethylcholine receptors, adenosine, dopamine, serotinin
[image] |
|
|
Term
|
Definition
move substances against their concentration gradient
requires energy via:
1. hydrolysis of ATP
2. coupling the transport of one molecule down its concentration gradient and harvesting energy to move another against its gradient via symports--piggy backing or anti ports) |
|
|
Term
| Na-K-Cl cotransporter (NKCC) |
|
Definition
symporter
moves 1 Na, 1 K, 2 Cl in same direction
high expression in kidney to mediate reabsorption |
|
|
Term
|
Definition
use ATP hydrolysis to move substances up concentration gradient
eg. Na/K pump (3 Na out, 2 K in)--ATP hydrolysis and conformational change to allow transport
25% of ATP reserves are spent on transport, allows the cell to create gradients that are central to many body functions (conduction of neuron signals, cardiac contraction) |
|
|
Term
| Nernst Potential of an Ion |
|
Definition
indicates what the membrane potential would be if the distribution of the ion across membrane reached equilibrium
the existence of membrane potentials is indicative of the presence of a ion selective transporter |
|
|
Term
|
Definition
a hemichannel structure which provides direct coupling between adjacent cells allows cells to communicate and transduce signals quickly eg. in cardiac muscle for synchronous contractions
[image] |
|
|
Term
| Goldman-Hodgkin-Katz voltage equation |
|
Definition
| gives membrane potential at which no net current flows= resting potential of cell w/o pumps
P≡uβRT/aF
u=ionic mobility
β=partion coefficient
a= membrane thickness |
|
|
Term
| Equilibrium Potential at Resting Potential |
|
Definition
in resting condition, conductance of the membrane is dominated by potassium-selected current as a result of:
1. potassium ions are unevenly distributed by pumps
2. leakage of potassium ions from inside to outside cell |
|
|
Term
| Membrane Potential of Cell |
|
Definition
is set by the combined effects of the electrochemical gradients of K, Na, Cl
combined conductance calculated by GHK |
|
|
Term
| graded potentials vs. action potentials |
|
Definition
graded: linear, change in potential is proportional to the current injected
governed by Ohm's Law V=RI
action potentials: all or none event. response is not proportional to the current injected. what really matters is that depolarization is enough to cross the threshold. amplitude of each potential is independent of original stimulus and only proportional to the amp of Na current that generates it |
|
|
Term
|
Definition
when open allows Na to flow inward
4 repeat motifs each with 6 transmembrane spanning regions
S4 segment is enriched in (+) amino acids and acts as voltage sensor
opening of the change generates the depolarizing current of action potentials |
|
|
Term
|
Definition
tetrameric
can be sustained or inactivating current
allow for the outward flow of K+
cause the depolarizing and deactivation portion of action potential |
|
|
Term
|
Definition
high ionic selectivity due to ionic binding on multi ion channels
High thresholds: L, N, P/Q types
Low Thresholds: T type (used by heart)
mostly present in action potentials in the heart |
|
|
Term
| activation of action potential |
|
Definition
process by which a channel is opened by a stimulus
stimulus causes the Na gates to open and flow inward to the cell |
|
|
Term
| Deactivation of action potential |
|
Definition
process of the closing once the stimulus has been removed
Na gates close, but this causes K to open and flow outward |
|
|
Term
| Inactivation of action potential |
|
Definition
closing of the channels while the stimulus is still present
models: Ball and chain inactivation model
when channel is open the ball binds to the inner mouth of the channel and blocks the pore |
|
|
Term
|
Definition
used equivalent circuit as analogy to explain electrophysiological properties of a cell (kind of like a battery)
membrane provides capacitor, channels are resistors, batteries are proton gradients |
|
|
Term
| Action Potential of a Cell (synopsis) |
|
Definition
1. stimulus added and cross threshold
2. Na channels open and move in= increase voltage
3. quickly inactivate and Na channels close
4. K channels open and move in=decrease voltage 5. Go down, past threshold=refractory period
the movement of Na and K is a result of them trying to reach their Nernst Potential |
|
|
Term
| Action Potential of a Cell Detailed |
|
Definition
|
|
Term
| Types of Leakage Conductance |
|
Definition
1. window (voltage gated channels)
2. intrinsically open (KCNK)
3. ligand gated channels (brain tonic currents w NT)
4. gap junctions (cardiac muscle) |
|
|
Term
|
Definition
posstium-selective leakage channels
leakage of K in response to its Nernst Potential
=are intrinsically open |
|
|
Term
|
Definition
|
|
Term
|
Definition
act by binding to specific receptors, especially GABAa, but KCNK receptors are likely the general target
work to alter the neuronal resting potential, input resistence, and membrane time constant |
|
|
Term
|
Definition
BDZ (used for anti-epileptic, anxiety)
barbituates |
|
|
Term
|
Definition
act on the GABAa receptor
GABAa receptor and increases the probability of Cl entering the cell, decreasing the charge in the cell and hyperpolarizing it
=makes it more difficult for the cell to generate an action potential
used to treat anxiety, hypnotic, muscle relaxant, epilepsy
eg. alprazolam (Xanax)
chlordiazepoxide (Librium)
diazepam (Valium)
lorazepam (Ativan). |
|
|
Term
|
Definition
Binds to GABAa receptor to sustain the opening of channel and allow more influx of Cl into the cell, decreasing charge in cell and hyperpolarizing it
=more difficult to generate an action potential |
|
|
Term
|
Definition
electrical hyperexitability of neurons BDZ increases the efficacy of inhibitory transmission and reduces the neuronal excitability and controls seizures
(work by increasing Cl- entrance into cell therby sending cell into deeper polarization) |
|
|
Term
|
Definition
| rare heart rhythm disorder that makes fast chaotic heartbeats results from mutation in K channel KCNQ1 that causes a reduction in Iks current and prolongs cardiac action potentials |
|
|
Term
| hypertension & cardiac arhythima and calcium channels |
|
Definition
mycoradial and smooth muscles in the heart need Ca to contract
reduction of Ca channels reduces their ability to contract and conduction through AV node |
|
|
Term
|
Definition
Ca permeable with polymodal activation properies (multiple things activate it)
TRP are cellular transducer activated by stimuli
their activation may explain similarity between pain and heat sensation (burning pin)
TRP used for pain treatment |
|
|
Term
| familial hemiplegic migraine (FHM) and calcium channels |
|
Definition
mutation in cav2.1 subunit makes phenotype of FHM that is triggered my head trauma deep coma, and cerebral edema
mutation produces shift in voltage dependence of activation and reduction of the inactivation of Ca current |
|
|
Term
|
Definition
Nifedipine (Adalat, Procardia)
Verapamil (Calan, Isoptin)
Diltiazem (cardizem)
acts of Ca+ channels |
|
|
Term
|
Definition
|
|
Term
|
Definition
BDZ (Valium, Xanax, Tranxene, Halicon, Librium, Ativan)
acts of GABAa receptors with transport of Cl- |
|
|
Term
|
Definition
Lidocaine, Verpamil, Diltiazem
acts of K channels (LQT on KCNQ1) |
|
|
Term
| Drugs for Cerebral ischemia |
|
Definition
Nimodipine (Nimotop)
acts on Ca+ channels |
|
|
Term
|
Definition
Conotoxins
acts on Ca+ channels (TRP) |
|
|
Term
|
Definition
General: Halothane, Isoflurane
Local: Lidocaine
Haltohane lamocortical neurons-where KCNK channels are highly expressed--involved in wakefulness
acts on K+ channels, allowing it to exit cell, making cell more negative and
making it more difficult for a action potential to occur |
|
|
Term
| overall properties of the cytoskeleton |
|
Definition
supports large volume of cytoplasm
dynamic cell crawling, muscle contraction, mitosis--all involved rearrangements
transport cargo, position organelles, motors move on their tracks
linke to cancer-altered cell polarity, elimination of contract inhibition and uncontrolled cell division
actin+vimentin+tubulin accour for MOST of the protein in the cell |
|
|
Term
|
Definition
These are coiled-coil proteins with an N-terminal head and a C-terminal tail.
toughest cyto filaments as it protection against mechanical stress
many different types that make a protein family vimentins and keratin @ cell jxn
lamins maintain shape of nucleus
assembly is controlled by phosphylation |
|
|
Term
| epidermoysis bullosa simplex |
|
Definition
keratin is a type of intermediate filament that holds the cells intact in resistance to a force
w/o this will have IF disease: epidermoysis bullosa simplex
-severity depends on mutation within the keratin |
|
|
Term
|
Definition
protect the structure of the nuclear membrane
type of IF that helps maintain structural integrity of nucleus around the membrane
laminas are entirely desstruced for cell division an rebuilt after |
|
|
Term
|
Definition
IF disease
caused by mutation in lamina series
progenia is an aging model and effects children
splicing machinery in cell that cuts mRNA into pieces depending on cell type and silent mutation G6008 |
|
|
Term
|
Definition
stiff, hollow tubes
formed from alpha/beta tublins dimers=protofilaments
fxn: long range structural integrity, cilia & flagella, mitosis |
|
|
Term
| microtubule polymerization properties |
|
Definition
GDP @ (-) end = depolymerize
GTP @ (+) end = polymerize
GTP gets hydrolyzed as (+) grows away from it
have a GTP cap at the (+) end where GTP tubulin has added to the MT
if cap is disrubed or slowed down you get GDP tubulin at the (+) end=depolymerizes |
|
|
Term
|
Definition
if get GTP cap disruption or slow down, get GDP tubulin at the (=) end= depolymerizes
MT use this property to find cappers for search and capture |
|
|
Term
|
Definition
| MT polymerize at (+) end and simultaneously depolymerize at the (-) end |
|
|
Term
|
Definition
The centrosome, which is the microtubule-organizing center
amorphous matrix with gamma-tubulin inside--acts a lock washer, clap for the GDP minus ends
even when anchored in centrosome, the MT are still dynamically unstable, growing and drinking at (+) end |
|
|
Term
|
Definition
can be centrosome, spindle fiber, or basal body of a cilium
act as a gap to prevent depolymerization by capping the minus GDP ends
“organized” MT eat up most of the tubulin, preventing MT from polymerizing randomly in the cell. Results in a highly organized network. |
|
|
Term
|
Definition
MT use dynamic instability to find cappers, chromosomes, etc in the cell
this controls cell length, polarity, and shape |
|
|
Term
|
Definition
proteins that bind MT, protect from depolarization and therefore stabilize them, promote assembly, or connect MT to capping proteins
eg. Tau involved in Alzhimers dieases--tangling of MT |
|
|
Term
|
Definition
dynamic MT cappers
higher affinity for (+) end
anchor MT in the ER and help with "search and capture" to set up the mitotic spindle
MT search with +TIPS at the (+) end until they find the kinetochore or edge of the cell, thereby anchoring the MT
constantly bind and let go= movement and exert force of kinetochore and cell membrane |
|
|
Term
| Actin and its polymerization |
|
Definition
flexible and short
minoris in form of a helix
involved in cell strux, cell crawling and division, strux of microvilli, contractile ring for cell division
use ATP because its more plentiful in in the cell and actin is the most abundant
ATP binds at barbed sid and ADP at pointed |
|
|
Term
|
Definition
appearance and dynamics of actin dependent on its binding proteins
types: nucleators, cappers, depolymerizers, severers, crosslinkers, formins--similar to +TIPS |
|
|
Term
|
Definition
genetic disease caused by mutation of the Arp2/3 complex
causes children to have ischemia, immune deficient, platelet disorder, cancer |
|
|
Term
|
Definition
polymerizes at leading edge, and forms new anchorage that allows it to move forward
PROTRUDE-GRAB-PULL-AND RETRACT FROM REAR
inolved in cell anchorage and movement
metastatic cancers use this mechanism
lamellopdodia and filopodia also involved |
|
|
Term
|
Definition
involved in cell crawling and muscle contraction
move cargo along actin filaments by contracting the filaments against one another and can move cytoskeleton against PM for cell crawling |
|
|
Term
|
Definition
when calcium binds, it causes slight movement of troponin which moves out of the way for myosin head to find and do power stroke
tropmyosin also moves
Ca dissipates after the nerve signal is removed and myosin falls off and muscle relaxes |
|
|
Term
|
Definition
made Z disks which provide anchorage for actin, M line made of myosin
myosin filaments walk on the (+) end of actin can cause contraction by bulling actin and z-disk in
actin anchored by dystrophin in the basal membrane
defect in this causes muscular dystrophy |
|
|
Term
|
Definition
moves cargo on MT along with dyne ins
move to the (+) end while dyne ins to (-)
kinesin uses ATP to move forward
some proteins serve as adaptors between motor and cargo=one motor can bind many different cargos |
|
|
Term
|
Definition
involved with cargo movement with kinesin
binds to (-) end of MT while kinesin binds to (+)
has cargo binding and regulatory domains
dominate the movement of cilia (power stroke and swoop under)
AAA protein structural motif |
|
|
Term
cytoskeletal elements involved in mitosis
CENP-E |
|
Definition
CENP-E (kinesin) destabilizes MT from the (+) end as the MT moves from kinetochore to centrosome
CENP-E is shaving the MT off the kinetochore=MT shortening and drives chromosome segregation
chrosome segregation driven by MT depolymerization at (-) end
cytokinesis pinching off is mediated by actin |
|
|
Term
| proteins involved in organelle movement and cytoskeleton building |
|
Definition
kinesin, dynenin and myosin
are also attaché to IF and carry them out to where network is being rebuild and are tacked onto existing filaments
eg. melaophores |
|
|
Term
|
Definition
| drug that prevents new actin filaments from being polymerized |
|
|
Term
|
Definition
| cross link actions and microtubles and IF |
|
|
Term
|
Definition
G1, S, G2
=growth, development and DNA replication
marked by decondensed chromosomes, centrosomes |
|
|
Term
|
Definition
intact nuclear envelope
miototic spindle forming
condensing chromsomes |
|
|
Term
|
Definition
nuclear envelope break down
chromosome in active motion
centrosome at spindle pole |
|
|
Term
|
Definition
chromosome aligned on equator
kinetechore MT attach sister chromosomes to separate poles |
|
|
Term
|
Definition
Kinechore mT shortens
spindle por moves outward=chromosomes seperation |
|
|
Term
|
Definition
daughter chromosomes at poles and condense
new nuclear envelope develops
end of mitosis
division of cytoplasm with assembly of contractile ring (actin) |
|
|
Term
|
Definition
| cytoplasm divided into 2 by contractile ring of actin and myosin |
|
|
Term
| Regulation of CDK-1 for Mitosis |
|
Definition
|
|
Term
|
Definition
protein involved in activation of mitosis
checkpoint to make sure everything is okay to proceeded from Interphase to Mitosis |
|
|
Term
|
Definition
ligand that binds to CDK-1
when bound to Cdk, triggers mitosis. Degraded at the end of mitosis (M Phase)
when bound to CDK-1 with correct phosphylations it can activate and allow mitosis to proceed |
|
|
Term
|
Definition
| when bound to Cdk, triggers DNA replication machinery. Degraded at the end of replication (S phase) |
|
|
Term
|
Definition
CDK activating Kinase
phosphylates CDK-1 at the same time Wee-1 does to support the activation of CDK |
|
|
Term
|
Definition
Cdk inhibtory kinase, adds an inhibitory phospate group on Cdk1 at the same ti CAK to keep Cdk1 in active form.
gets Negative feeback from an active Cdk1 |
|
|
Term
|
Definition
activated by a phosphate
works to activate a Cdk1 that has both an inhibitory and activating phosphate.
Removes the inhibitory phospate.
Regulated by Postive feedback from an active Cdk1 |
|
|
Term
|
Definition
| a cyclin-dependent kinase inhibitor (CKI) that inactivates an active Cdk1 by binding around the Cdk1-cyclin complex |
|
|
Term
| Anaphase Promoting Complex |
|
Definition
Checkpoint to make sure chromosomes have lined up correctly on the metaphase plate
Protessin keeps the sister chromatids stuck together
The cohesing needs to be removed by seperase for anaphase to proceed Ubiquitinlyation and
degration of securin activates the seperase to remove the cohesins that hold chromatids together
[image] |
|
|
Term
|
Definition
| Cdc20: activates APC to promote anaphase |
|
|
Term
|
Definition
Anaphase Promoting Complex
when active it ubiquitlates and degrades securin which when bound to seperase, keeps it inactive
by removing securin, seperase can separate sister chromatids |
|
|
Term
|
Definition
| when activated it removes the cohesion mechanism of protessin in order for anaphase to proceed |
|
|
Term
|
Definition
keeps sister chromatids connected,
removed by seperase for anaphase to proceed |
|
|
Term
|
Definition
bound to seperase and keeps it inactive and unable to remove protessin and have sister chromatids separate for anaphase
degraded and ubuiquitlated by APC |
|
|
Term
|
Definition
possible games (2^23 > 8 million) independent assortment and law of segregation
[image] |
|
|
Term
|
Definition
happens at prophase of meiosis I
formation of chiasma |
|
|
Term
|
Definition
| segregates fans of replication, transcption, RNA processing, ribosomal biosynthesis (rRNA in nucelous) |
|
|
Term
|
Definition
| double membrane, continues with lumen of ER, composed of lamin (IF), disassembled during pro metaphase-- regulated by phosylation of the laminas |
|
|
Term
|
Definition
| cans tandem copies of heterchromatic receptive elements, needed for segregation of chromosomes, site of kinetochore assembly, site of chromatid cohesion with help of protessin |
|
|
Term
|
Definition
| stx that forms at the centrosome, site of spindle attachment, need for segregation of chromosomes |
|
|
Term
|
Definition
repeats at 3' end of chromosome to prevent loss during DNA replication
regulation of teleomere length implicated in aging as well as cancer |
|
|
Term
|
Definition
beads of a string
made of H2A, H2B, H3, H4
linker DNA associated with H1 |
|
|
Term
|
Definition
longest and variable part of cell cycle
has important start or restrict check points |
|
|
Term
|
Definition
phase when DNA replicated
X inactivation occurs |
|
|
Term
|
Definition
prepares cell for mitosis chromosome condensation makes the end of G2
cell enlarges and doubles in mass
RNA & protein synthesis |
|
|
Term
|
Definition
| some specialized cell such as neurons and skeletal muscle stay in this phase for a lifetime |
|
|
Term
|
Definition
| part of G1 that test if the environment is favorable for the initiation of cell division |
|
|
Term
|
Definition
| ensures DNA damage has been repaired before DNA replication happens |
|
|
Term
|
Definition
| wants to make sure all DNA has been replicated and damage has been repaired |
|
|
Term
|
Definition
| ensures that chromosome is aligned correctly before anaphase occurs |
|
|
Term
|
Definition
location of DNA is central to expression of the genes
genes that are more transcribed/expressed are on the core of the DNA while those that aren't are on periphery |
|
|
Term
| higher order chromatin structure |
|
Definition
| chrosomes are tightly bound to proteins of two general classes:
histones and nonhistone chromosomal proteins.
Chromatin = DNA and associated proteins
DNA is acidic, histones are basic– they neutralize negative charge on DNA
=important for condensing the chromatin
chromatin: 1/3 DNA, 1/3 Histone, 1/3 non-histone protines
[image] |
|
|
Term
|
Definition
aka solenoid
made of histone octomer (H2A, H2B, H3, H4)
H1 neutralizes linker DNA allows 30nm fiber to form
2 turns of DNA around each nucleosome |
|
|
Term
| euchromatin vs. heterochromatin |
|
Definition
euchromatin: expressed regions of DNA
loosely wound--lighter staining
replicated early
heterochromatin: not expressed as often (teleomeres, centromere)--darker staining
replicated late
tightly bound
involved in looping |
|
|
Term
|
Definition
Chromosome scaffold composed of: Topoisomerase II
SMC (structural maintenance of chromosomes) class proteins including condensin and cohesin
Scaffold attachment regions (SARs) A
T-rich region of DNA
Topoisomerase II sites
[image] |
|
|
Term
| nuclear recognition signal |
|
Definition
Tag on protein which signals it to be inserted into the nucleus
recognized by nuclear import receptors--different types for various specificity |
|
|
Term
| Molecular Switch for Nuclear Transport |
|
Definition
|
|
Term
|
Definition
|
|
Term
| nuceloside vs. nucleotide |
|
Definition
base at C1 with base joined with glycosidic bond
base with base at C1 and phosphodiester bond at C5 |
|
|
Term
|
Definition
between 5' and 3'
are close range H bonds
side chains must extend out from phosphate backbone to allow bonds to form |
|
|
Term
| disruption to DNA hybridization |
|
Definition
| disruptions in complementary bonding, reduce Tm of a DNA |
|
|
Term
|
Definition
A: similar to B but has a hybrid of RNA in it a
B: most common anti parallel R handed alpha helix
Z: twisted left handed helix that requires alternating Pur and Pyr sequence |
|
|
Term
|
Definition
the degree of coiling is the writhe
causes DNA to be compacted
DNA needs to be uncoiled in order for enzymes to access the bases
negative supercoiling (action of DNA gyrase) utilized to access DNA for replication and transcription |
|
|
Term
|
Definition
alter the supercoiling of DNA by cleavage strands through the break, and resealing.
Type 1: alters one strand
Type 2: alters both strands (gyrase)
does so in a concerted action |
|
|
Term
| Nalidixic acid and novobiocin |
|
Definition
| antibiotics that interfere specifically with bacterial topoisomerases/gyrases. |
|
|
Term
| Doxorubicin and etoposide |
|
Definition
inhibit eukaryotic topoisomerases
and are used as chemotherapeutic agents. |
|
|
Term
|
Definition
utilized to access DNA or tighten the winding of DNA around the histones
particular combinations of histone modifications comprise a “histone code” for active vs. inactive chromatin
Methylation makes it more wound up--> heterochromatin
Histone acetyltransferases can transfer acetate groups to lysine residues in the N-terminal tails of histones,
= "loosening” chromatin structure and promoting gene transcription.
serine phosylation= gene activation |
|
|
Term
| Histone acetyltransferases |
|
Definition
| adds acetate groups to lys residues to N terminus of histones to loosen its binding to DNA and making accessible for replication or transcription |
|
|
Term
| histone serine phosphylation |
|
Definition
posy of serene 10 in H3
=gene activation |
|
|
Term
|
Definition
winds the DNA tighter
= less expressed (heterochromatin) |
|
|
Term
|
Definition
| huge enzyme complex that catalyses addtion of nucelotides to the 3’ OH end of DNA Synthesis is 5’ to 3’ (unidirectional) In order to add, there needs to be a primer (3’ OH) for DNA polymerase to act |
|
|
Term
|
Definition
| after primase adds the RNA primer, this initiates initial synthesis on leading or lagging strand |
|
|
Term
|
Definition
DNA repair
(exonuclease activity) |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
primase adds RNA primer
DNA polymerase α intiates the synthesis of DNA
DNA polymerase δ synthesizes lagging strand until end of Okazaki Fragment
repeat for next fragment
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Term
| proteins at the replication fork |
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Definition
primase: adds RNA primer so that synthesis can begin at a 3' OH
helicase: unwinds the DNA and makes it accessible for the DNA polymerase
SSB: prevents the single DNA strand from binding to itself
DNA Gyrase: introduces negative supercoils to relieve the winding introduced by helices |
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Term
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Definition
uncoding tandem repeats ~1000 bp sequence (TTAGGG) that are at the ends of lagging strand
Added in newly synthesized DNA to ensure ends of DNA are preserved
as we age, telomeres get shorter and shorter
cancers have activated telomerase activity when not supposed to for indefinite growth |
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Term
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Definition
only expressed in germ lines and stem cells
synthesizes the telomere sequences with reverse transcriptase activity
telomerase provides an RNA template for repeating DNA sequence--> reverse transcriptase activity
Then use the new telomere seq as a primer to add in the gap
results in a 3' overhanging that binds to proteins |
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Term
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Definition
Telomerase is expressed in germ line and stem cells, not in most other cells.
Lack of teleomerase activity results in DNA shortening at each DNA replication
Most cancer cells, although of somatic origin, have activated telomerase expression, allowing them to divide indefinitely. |
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Term
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Definition
10^4 purines/cell/day lost due to thermal disruption
Link b/w purine and sugar is unstable |
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Definition
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Term
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Definition
| UV causes adjacent thymine to dimerize |
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Term
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Definition
| replace one purine with another, or one pyrimidine with another |
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Term
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Definition
replace a purine with a pyrimidine, or vice versa.
A G<-->C or T |
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Term
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Definition
3’-5’ exonuclease activity of DNA polymerase provides a proofreading
DNA repair nucleases can recognize and excise single strand region containing abnormal nucleotides
1. exonucelase
2. DNA polymerase fills in
3. DNA Ligase seals |
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Term
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Definition
| recognize and excise single strand region containing abnormal nucleotides (thymine dimers, altered bases) |
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Term
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Definition
part of DNA repair
cleaves nucleotides that have lost their base at the adjacent phosphodiester bond
DNA pol and ligase finish off repair process |
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Term
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Definition
recognize altered bases and remove them by cleaving the glycolytic bond.
The AP endonuclease system can then repair. |
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Term
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Definition
5% of C (cys) are methylated
deamination of it converts C-->T = TG pair instead of CG
usually deminations would cause the formation of a abnormal base, but in this case cell can tell if its the T or G that is mismatched
specific DNA glycolase recognizes TG mismatches and specifically removes the T
=sometimes its right and sometimes wrong so cys-methylation still accounts for 1/3 of mutations in humans |
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Term
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Definition
autosomal recessive disease related to DNA mutation
causes sensitivity to light--> cancer develops on skin
patients are unable to repair thymine dimers from UV irradiation |
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Term
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Definition
stunted growth
UV sensitivity
defective DNA helicase |
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Term
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Definition
premature helicase
graying, catatracts, osteoperosis
Werner's gene encodes for helices that is involved in repair |
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Term
| Hereditary nonpolyposis colorectal cancer |
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Definition
mutations in genes involved in DNA mismatch repair
(glycolase, AP endonuclease, DNA repair nucleases) |
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Term
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Definition
| short interspersed nuclear elements repeats dispersed throughout the genome Alu repeats account for ~5% of genome and can move in the genome |
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Term
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Definition
long interspersed nuclear elements
type of repeat DNA sequence dispersed in the genome
duplicate by transposition by retrotranposons that can move |
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Term
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Definition
~10% of genome is DNA repeats
most localized at centrosomes and heterochromatin
SINEs; Alu repeats
LINEs: translocate with retrotransposons
rRNA found in tandem repeats |
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Term
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Definition
long noncoding RNA
involved in numerous levels of gene regulation |
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Term
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Definition
σ: recognizes the promoter and initiates RNA synthesis
α: assemble exzyme and bind regulator proteins
β: binds nucleotide triphosphates and forms phosphodiester bonds
β': binds DNA template
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Term
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Definition
sequences in DNA that allow RNA polymerase to bind
located immediately upstream the transcription start site
The precise sequences of different promoters alter the efficiency that RNA polymerase alpha can bind
Different a subunits can recognize different promoters with different efficiencies. |
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Term
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Definition
sigma subunit binds and initiates the making of RNA
a short transcript, sigma is released (aborts), and then full length RNA is synthesized by the rest of RNA polymerase |
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Term
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Definition
common terminator of RNA synthesis in proks
its is a structure fold |
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Term
| Transciption in proks vs. euks |
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Definition
transciption and translation occurs simulatenously in proks (more prone to error than euks that separate and proofreads)
euks make use of RNA polymerase I, II, III to make different types of RNA transcripts
euks have RNA processeing (capping, A tail, splicing) |
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Term
| RNA Polymerase I, II, II products |
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Definition
I: rRNA
II: mRNA, hnRNA, miRNA
III: tRNA, rRNA |
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Term
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Definition
| mushroom toxin that binds to RNA polymerase II and blocks elongation of RNA transcript |
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Term
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Definition
TATA box (recognized by TFIID)
GC box
CAAT box
TF neeed to bind and recognize promoter regions
TF can be general or specific (for a particular set of genes) |
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Term
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Definition
| RNA poly need transcription factors in order to find the beginning of a sequence to be transcribed, can be general or specific |
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Term
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Definition
| transcription factor that recognizes and binds to TATA box, elk promoter regions |
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Term
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Definition
transcription factor which phosylyates RNA polymerase II
=promoting/activating it for transcription |
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Term
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Definition
regions upstream of promoter that allows regulatory proteins to bind and support the beginning of transcription
can bind far away and loop over to the promoter region and have an effect |
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Term
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Definition
| can increase or decrease transcription (activators or repressors) |
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Term
| processing of pol II transcripts (mRNA, hnRNA, miRNA) |
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Definition
capped by addition of 7-methyl guanosine residue at 5' polyadenlyation at 3' important for stability and regulation of translation interaction between 5' cap and 3' tail help with efficiency of recruitment of ribosomal pre-intiation complex
shorter poly A tail leads to less translation of mRNA transcript |
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Term
| polysictronic vs. monsictronic |
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Definition
| proks tend to have mRNA transcripts that encode for multiple genes, while euk transcripts encode for a single protein |
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Term
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Definition
all poly II transcripts are processed (mRNA, hnRNA, miRNA)
remove introns and link extrons |
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Term
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Definition
part of RNA transcript that are removed in the processing
removal catalyzed by spilcesomes
have sequences that code for their precise removal
The conserved A within the intron functions as a branch point during the splicing reaction |
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Term
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Definition
catalyze RNA splicing with snRNP
U1: binds 5' splice site
U2: binds branch site (A)
U5: binds 3' splice site
U4/6: spilceosome assembly |
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Term
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Definition
after spliceosome has been assembled by U4/6
1. 2' OH of branch site A attacks the 5' splice site
2. creates a lariat structure =branch site now has its normal 3' and 5' phosphodiester linkage and now a 2' phosphodiester linkage to the 5' splice site
3. 3'OH of the first exon cleaves the 3' splice site and forms a phosphodiester linkage to the second exon
4. lariat ie excised and degraded
[image] |
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Term
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Definition
made by RNA poly II
Drosha and Dicer cleave miRNA
can then bind to RISC (RNA-induced
silencing complex) and prevent their translation |
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Term
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Definition
| Short RNAs are important for mRNA degrdation, translation inhibition and gene silencing |
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Term
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Definition
made by RNA poly I and III
transcribed from tandem RNA repeats
Precursor rRNA is processed into the mature 18S, 28S, and 5.8S rRNAs by specific nucleases |
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Term
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Definition
makes small RNA, esp 5S rRNA and tRNA
needs TFIIA-C (A, B, and C) to do its transcription |
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Term
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Definition
-Cleaving 5’ leader
-Splicing with endonuclease
-Removal of 3’UU and replace with CCA
-Modification of specific bases |
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Term
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Definition
involved in translation Variation in 3rd base
There is wobble in 3rd position first base of anticodon can only pair with certain 3rd base codon 8/16 or 1/2 cases, the 3rd position base is non-definitive
= speeed up rate of base pairing or mechanism of translation Protection against errors
without this there would bes less efficiency in protein translation
it also provides regulation for translation (less mistakes) |
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Term
| aminoacyl-tRNA transferase |
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Definition
there are 20 of them involved in attaching a.a. to tRNA
They specifically recognize and bind a tRNA and an amino acid.
1) adenylation (activation) of the amino acid utilizing ATP
2) transfer of the adenylated amino acid to 3' OH of tRNA, release of AMP |
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Term
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Definition
| translation in proks is initiated by this amino acid |
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Term
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Definition
| inhibits transition from initiation to elongation and causes miscoding. |
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Term
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Definition
| binds to small ribosomal subunit and inhibits binding of aminoacyl-tRNAs to A site. |
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Term
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Definition
| nhibits peptidyl transferase activity of large subunit. |
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Term
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Definition
| binds to large subunit and inhibits translocation. |
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Term
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Definition
inhibits peptidyl transferase activity
of large subunit and translocation. |
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Term
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Definition
A single 21 kd fragment can kill a cell.
It catalyzes ADP-ribosylation of EF2 using NAD+,
blocking the translocation step of protein synthesis |
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Term
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Definition
set of alleles on the same chromsomal factor that are transmitted together
Can treat them almost a if they are an allele
A haplotype may be one locus, several loci, or an entire chromosome depending on the number of recombination events that have occurred between a given set of loci.
haplotype is a set of single-nucleotide polymorphisms (SNPs) on a single chromosome of a chromosome pair that are statistically associated. These associations allow one to use just a few alleles as the ID of an entire halotype ot identify all other polymorphic sites in the region of th halotype
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Term
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Definition
| unique set of alleles on the same chromsomal factor. Can treat them almost a if they are an allele. It is present in a significantly higher frequency among affected compared to control individuals |
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Term
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Definition
| direct biological action that increases susceptibility to that disease. it is in linkage disequil with another allele of the gene or a nearby gene that increase ones susceptibility to that trait |
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Term
| TDT (Transmision Disequibilibrium Test) |
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Definition
| comparing affected chromosomes to non affected chromosomes--essentially measuring the impact on the child in question--it is family based and has not population strategy |
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Term
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Definition
multiple testing corretion for a genome wide linkage scan already taken into account
when making a calculation you assume linkage occurs and doesnt occur |
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Term
| Corrections for Multiple Testing |
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Definition
LOD >3
Bonferroni Correction
Determine signifcane with simulation or permutation studies
False Discovery Rate (FDR) |
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Term
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Definition
Short Tandem Repeat P (SNRP)--microsattelites
SNP: single nucelotide polymorphism
CNV; copy number variation |
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Term
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Definition
short tandem repeat polymorphism
2-4 bp seq that are repeated a variable # of times
- high herterogozity
- high mutation rate
- not easily automated
- ideal for genome linkage scans
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Term
| SNP (single nuc polymorphism) |
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Definition
single base pair mutation that creates two forms of a DNA sequency nd has a freq of more than 1%
it is essentially any location in the genome that changes and makes a precursor for a change in the population
most common source of genetic variation in humans
Low hterogoz
low mutation
easily automated
ideal for making halotypes |
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Term
| synonomous vs nonsynon variants |
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Definition
types of SNPs
nonsynon: will change the a.a. sequence of proteins very common and low frequency variants
Synonymous: in coding region but dont change the a.a. coded for |
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Term
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Definition
type of SNPs
are not in protein coding sequence
my still impact gene expression
are the most high frequency variants |
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Term
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Definition
copy number variants
deletions, insertions, duplications, and complex genomic rearrangements
- accounts for about 10% of geneome
- dont conform to HW
- difficult to genotype
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Term
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Definition
| a measure of association of alleles on a chromosome. two loci are in linkage diseq when their alleles are not randomly associated |
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Term
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Definition
| meausure of linkage disequibilirum squared correlation coeffient between the presence and absence of alleles at different loci |
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Term
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Definition
| subset of SNP that account fo the amjority of genetic variation in a gene fragment |
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Term
| parametric vs nonparametric analysis |
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Definition
linkages: non independent seg of families of genes at two or more loci on the same chrom
parametric: assume explict mode of inheritene, Mendeliant Traits (powerful0
Nonparametric: no assumption about the mode of inheritance (less powerful and doesnt work well for complex fmilies bc it has too much heterogenity) |
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Term
| Qualtiative Traits vs. Quantitiative Traits |
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Definition
Qualitative: sets a threshold for which someone either has disease or does not (dichotomy)
Quantitative: disease is measured in a continuous fashion (height, weight, bp) |
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Term
| genetically complex trait |
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Definition
phenotypic trait that exhibit evidence for familial aggregation and genetic involvement but is not inherited in an easily determined manner
they are polygenic and multifactorial |
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Term
| Exceptions to Menedelian Inheritance |
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Definition
trinucleotide repeat disorders
mitochondria disorders
imprinting |
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Term
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Definition
one allele inherited in an autsomal dominant manner
the second mutated in somatic fashion
:: process of developing tumors is kind of recessive bc need predisposition gene AND a second hit/mutation to occur within a somatic cell |
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Term
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Definition
have the affected gene but not phenotypically affected and able to pass on the gene to progeny.
need some other minor and modifier genes in order to phenotype to develop |
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Term
| de novo germline mutation |
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Definition
| germ line mutation pass o to subsequent generations |
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Term
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Definition
| mutations in 2 copies of the gene but they are distinct, different mutations. 2 mutations types |
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Term
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Definition
| unaffected female carries the mutation but does not express disease. only expressed in males but not carried on X...more a result of the physiology of being a particular sex |
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Term
| trinculeotide repeat disorder |
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Definition
| the greater the expansion the earlier the onset |
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Term
| trinculeotide repeat disorder |
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Definition
| the greater the expansion the earlier the onset |
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Term
| chaperones role for misfolded proteins |
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Definition
if a glycoprotein is misfolded a chaperone will:
1. attempt to re-glycosylate the protein so it may fold correctly
2. help break misfolded bonds
3. if unsuccessful, the chaperone will export the protein for degradation in the cytosol
eg. of such a chaperone is CALNEXIN |
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Term
Things involved in vesicle movement
1. ER--> cis Golgi
2. trans golgi--> lysosomes
3. cis golgi--> ER |
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Definition
1. Sar & COPII
2. Mannose-6-P (receptor recruits coating proteins) & AP1 + clathrin
3. Arf (retrograde transport of lumenal ER proteins with KDEL sequence that bind to receptor in cis Golgi)& COP I |
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Term
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Definition
I HURL when TAY GAUCH PICKS his nose
I cells
Hurlers
Tay-Sachs
Gauchers
Wierner-Picks |
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Term
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Definition
Zellweger
Xlinked dystrophy |
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Term
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Definition
1. 3 Na ions bind to pump
2. ATP phosphylates the pump, causing a conformational change
3. Na ions released to the outside of the cell
4. 2 K ions bind to the pump
5. Dephospylation of the pump causes a conformational change
6. K ions are released to the cytosol |
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Term
| Differences between cardiac and neuronal potentials |
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Definition
-cardiac initial input is from an AV sinus wave vs from a neurotransmitter from the pre-synaptic neuron
-the plateau phase in the cardiac action potential is much longer than in nueronal cells
-The cardiac action potential is much longer than the neuronal action potential |
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Term
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Definition
[image]
regulation of actin cytoskeleton
it is the site of nucelation for actin filaments
the growth of the filament is marked by branching and growth of a new actin at a 70 degree angle from its mother
it stimulates actin polymerization by creating a nuclear core
=action is useful for actin branching which is used for cell crawling
mutation=Wiskott-Aldrich Syndrome |
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Term
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Definition
[image]
during import: job of RAN-GTP is to help the receptor release the cargo. Then it helps the receptor find its way back out--> RAN-GDP when outside
during export: job of RAN-GTP is the help the receptor bind with its cargo. Once it gets to surface turns to RAN-GDP and says PAYCE! lets the receptor find its own way back into cell |
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Term
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Definition
mitotic inhibitor used as a chemotheraphy drug to treat cancer
stabilizes microtubules and as a result, interferes with the normal breakdown of microtubules during cell division
=stopping cancer cells from dividing rapidly |
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Term
| difference between myosin and kinesin |
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Definition
| myosin releases the cytoskeleton for movement while kinesin always has one head attached |
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Term
| G1 Restriction Checkpoint |
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Definition
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Term
| DICER, DROSHA, miRNA, and RISC |
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Definition
| DICER and DROSHA is the protein that cleaves dsRNA to form miRNA binds to RISC for RNAi (inhibition) |
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Term
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Definition
Q/G Bands: AT Rich, tissue specific, few genes found here, replicate later
R Bands: GC Rich, most genes encoded here, replicate early, Alu rich |
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Term
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Definition
its stalk is encoded with rRNA from end to end
microsatellite, small pieces of DNA repeats are distinguishable feature |
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Term
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Definition
a specific pattern of gene activation occurs in oogenesis and a differnt pattern occurs in spermatogenesis
mutations can result in uniparental disomy: Prader-Willi syndrom and Angelman syndrome |
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Term
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Definition
| when there are two cell lines which differ genetically but originated from a single zygote (X inactivation) |
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Term
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Definition
two chromosomes of a given kind are inherited from one parent
eg. getting both your mother's parental chromosome (both from grad dad) and none from your dad |
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Term
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Definition
two chromosomes of a given kind are inherited from one parent
eg. inheriting your mother's paternal and maternal chromosome, but nothing from your dad |
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Term
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Definition
inactivation either the maternal or paternal x chromosomes by 5-methylcytosine
methylation inhertited by maintaince methylase |
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Term
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Definition
regulatory gens/proteins
~60 amino acid longs it is a DNA sequence within a gene
involved in regulation patterns of anatomical development encode TF that turn on cascades of other genes
contains a homeodomain that allows it to bind to hox genes on the DNA |
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Term
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Definition
| clusters of homeobox genes that regulate spacial regulation of anatomical structures |
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Term
Examples of alternative splicing
IgM (B cells)
Gag & poly Gag (retrovirus)--frameshifts |
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Definition
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Term
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Definition
| abnormal number of whole chromsome set |
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Term
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Definition
abnormal number of individual chromsomes
eg. Turners, Klinfeters (loss of chromsomes) vs. Downs (extra chromsomome) |
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Term
| proportion/percentages of genome composition |
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Definition
unique single copy (75%)
Reptitive--SINEs & LINEs (15%)
encode proteins (10%)
Satallite (10%)
mini: help with identification of ppl bc so unique
alpha satelittes at centromeres |
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Term
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Definition
most common heritable form of mental retardation
associated with cytogenic fragmentation
chromatin doesnt condense at 27.3
carrier females may not be retarded |
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Term
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Definition
silence one of X chromsomes by methylation
aka X inactivation by 5-methylcytosine |
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Term
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Definition
| middle aged blindness caused by mutation in complex I |
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Term
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Definition
semiautonomous: imports some of its proteins from the nucleus
high evolution rate= more prone to mutations
mt used to ID closely related ppl= determines lineage |
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Term
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Definition
can have mutation and wild type within an individual
depending how how much of the gene is expressed, one may not have the phenotypic expression bc genes did not cross threshold
if some inherits a mutation they likely cross the threshold early and then express the phenotypical disease |
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Term
| mt replicatitve segregation |
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Definition
within a heterogenous individula able to give rise to daughter cells that have unequal distribution of mutated mitochondria genes bc it divides by fission
the random allocation of mt genome determines the severity of the genotype
basically the seveerity of a phenotype within an indivdual is due to sampling error or bottle neck effect |
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Term
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Definition
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Term
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Definition
| line by which two homologous alight |
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Term
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Definition
| the effects of one gene are modified by one or several other genes, which are sometimes called modifier genes |
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Term
| cross between to heterozygous individuals for two chromosomes |
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Definition
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Term
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Definition
differnt effect in males due to hormonal influences
--the experession of mutation is affected by the physicology of the body (eg. exposure to testosterone) |
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Term
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Definition
only expressed in 1 sex but not passed on by X and Y chromosome
genes which are present in both sexes of sexually reproducing species but turned on in only one |
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Term
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Definition
| p(A carrier) x p(B carrier) x p (homlogous mutant) |
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Term
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Definition
The homeodomain fold is a protein structural domain that binds DNA or RNA and is thus commonly found in transcription factors.[2][3] The fold consists of a 60-amino acid helix-turn-helix structure in which three alpha helices
eg. homeoboxes that bind to hox genes |
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Term
| linkage vs. linkage disequilibrium |
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Definition
linkage disequilibrium: occurrence of some combination of alleles or genetic markers in a population more often or less often than would be expected from a random formation of haplotypes from alleles based on their frequencies.
linkage: association of two or more loci on a chromosome with limited recombination between them.
The amount of linkage disequilibrium depends on the difference between observed and expected (assuming random distributions) allelic frequencies. |
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Term
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Definition
| non genetic conditions that mimick the phenotypes of a genetic disorder |
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Term
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Definition
different mutations in the same locus can cause a similar phenotype
eg. different mutations for CF |
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Term
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Definition
similar phenotype resulting from mutations at genetically different loci
eg. pathway that can have mutation at differnt locations but produces same mutated result |
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Term
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Definition
more than one phenotype caused by a single allelic mutation
eg. a mutation in chrom 1 which causes blindess, deafness, etc. |
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Term
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Definition
consist of SNP and short repetitive seq of variable lengths (microsatallietes)
cause phenotypic diversity |
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