Term
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Definition
Fatty acid oxidation
Acetyl CoA production
TCA cycle
oxidative phosphorylation |
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Term
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Definition
Glycolysis
Fatty acid synthesis
HMP shunt
Protein synthesis (RER)
Steroid synthesis (SER)
Cholesterol synthesis |
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Term
| Mitcochondria and Cytoplasm metabolism |
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Definition
Heme synthesis
Urea cycle
Gluconeogenesis |
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Term
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Definition
glycolysis- PFK-1
Gluconeogenesis- F-1,6-BP
TCA- Isocitrate dehydrogenase
Glycogen synthesis- glycogen synthase
Glycogenolysis- glycogen phosphorylase
HMP shunt- G6PD
Pyrimidine synth- CPS 2
Purine synth- Glutamine-PRPP-synthetase 2
Urea cycle- CPS 1
FA synthesis- acetyl CoA carboxylase
FA oxidation- Carnitine acyl transferase
Ketogenesis- HMG CoA synthase
Cholesterol synthesis- HMG CoA reductase |
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Term
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Definition
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Term
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Definition
Aerobic metabolism of glucose produces:
32 ATP- malate aspartate shuttle (heart and liver)
30 ATP- G3P shuttle (muscle)
Anaerobic glycolysis produces only 2 net ATP per glucose |
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Term
| Universal Electron acceptors |
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Definition
Nicotinamides (NAD from vitamin B3, NADP)
Flavin nucleotides (FAD from vit B2)
NAD is used in catabolic processes to carry reducing eq away
NADPH is used in anabolic processes as a supply of reducing equivalents
NADPH is a product of the HMP shunt; used in anabolic processes, resp burst, p450, glutathione reductase |
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Term
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Definition
Ubiquitous. High affinity (low km), low capacity.
Feedback inhibited by G6P, unindexed by insulin
"Can run off low amounts of glucose) |
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Term
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Definition
Within liver and B cells of pancreas
Low affinity, high capacity; induced by insulin
At low glucose levels, hexokinase sequesters it in tissue
At high glucose levels, glucokinase stores it in the liver |
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Term
| Glycolysis Eq require ATP |
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Definition
Glucose > G6P (hexokinas/glucokinas)
F6P > F-1,6-BP (PFK-1 *RLE)
"Anything with a 6, requires ATP" |
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Term
| Glycolysis Eq that produce ATP |
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Definition
1,3-BPG <> 3-PG (phosphoglycerate kinase)
PEP > Pyruvate (pyruvate kinase) |
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Term
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Definition
Fasting State: Inc glucagon > Inc cAMP > inc PKA > Inc FBPase-2, Dec PFK2, less glycolysis
Fed State: Inc insulin > dec cAMP > Dec PKA > dec FPBase2, Inc PFK2, more glycolysis |
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Term
| Pyruvate Dehydrogenase complex |
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Definition
Pyruvate + NAD + CoA > ACoA + CO2 + NADH
Needs cofactors:
NAD, FAD, pyrophosphate, CoA, lipoic acid (B1,2,3,5)
Complex is similar to a-KG dehydrogenase complex
*Arsenic inhibits lipoid acid - Vomiting, rice water stools, garlic breath |
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Term
| Pyruvate dehydrogenase complex deficiency |
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Definition
Causes backup of substrate > lactic acidosis
Most are due to X linked mutation in E1-a (su of PDC)
Neurologic defects, in infancy
Tx: intake of ketogenic nutrients, high fat or lysine/leucine |
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Term
| Alanine Aminotransferase (B6) |
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Definition
| Alalnine carries amino groups to the liver from muscle |
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Term
| Pyruvate carboxylase (biotin) |
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Definition
| oxaloacetate can replenish TCA cycle or be used in gluconeogenesis |
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Term
| Pyruvate dehydrogenase (b1, B2, B3, B5, lipoid acid) |
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Definition
| Transition from glycolysis to the TCA cycle |
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Term
| Lactic acid Dehydrogenase (B3) |
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Definition
End of anaerobic glycolysis
Major pathway in RBCs, leukocytes, kidney medulla, lens, testes and cornea |
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Term
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Definition
*Citrate is Krebs starting substrate for making oxaloacetate
OAA > citrate (citrate synthase)
Isocitrate > a-KG (isocitrate dehydrogenase)
aKG > Succinyl CoA (a-KG dehydrogenase)
10 ATP made per 1 acetyl coA |
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Term
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Definition
Isocitrate > a-KG
a-KG > succinyl CoA
Malate > OAA |
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Term
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Definition
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Term
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Definition
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Term
| ETC and oxidative Phosphorylation |
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Definition
NADH electrons from glycolysis enter via the malate aspartate or G3P shuttle. FADH2 electrons are transferred to complex 2
NADH = 3 ATP
FADH = 2 ATP |
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Term
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Definition
Directly inhibit electron transport causing dec proton gradient
Rotenone (c1), Cyanide (c4) Antimycin A (c3) and CO (c4) |
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Term
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Definition
Directly inhibit mitochondrial ATP synthase causing inc proton gradient
Oligomycin |
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Term
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Definition
Inc permeability of membrane. ATP synth stops, but ETC continues. Produces heat
2,4-DNP, aspirin, thermogenin (brown fat) |
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Term
| Gluconeogenesis irreversible enzymes |
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Definition
| Pyruvate carboxylase, PEP carboxylase, F-1,6-BP, G6P |
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Term
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Definition
In mitochondria
Pyruvate > carboxylase
Req: biotin, ATP
Act: acetyl CoA |
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Term
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Definition
In cytosol
OAA > PEP
Req: GTP |
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Term
| Fructose-1,6-Bisphosphatase |
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Definition
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Term
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Definition
In ER
G6P > Glucose
Lacking in Mm |
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Term
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Definition
Occurs primarily in the liver
Also found in the kidney, intestine
Dysfunction causes hypoglycemia
Odd chain FA can enter the TCA cycle as succinyl coA (from propionyl coA) and serve as a glucose source
Even chain FA cannot produce glucose |
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Term
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Definition
Provides a source of NADPH from G6P
Also yields ribose for nucleotide synthesis and glycolytic intermediates
All occurs in the cytoplasm
*no ATP used or produced
Lactating mammary glands, liver, adrenal cortex, RBCs |
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Term
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Definition
Oxidative (irreversible)
G6P > Ribulose-5-P and 2NADPH (G6PD *RLE)
Nonoxidative (reversible)
Ribulose-5-P > Ribose-5-P, G3P and F6P
(Phosphopentose isomerase, transketolases - Req B1) |
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Term
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Definition
Activation of membrane bound NADPH oxidase
O2 > O2* > H2O2 > HOCl
NADPH oxidase, SOD, myeloperoxidase |
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Term
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Definition
NADPH keeps glutatione reduced, which detoxifies free radicals and peroxidases
Dec NADPH leads to hemolytic anemia
Can be caused by fava beans, sulfonamides, primaquine, antituberculosis drugs
Heinz bodies - Oxidized hemoglobin precipitated into RBCs
Bite Cells - results from phagocytic removal of Heinz bodies by splenic macrophages |
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Term
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Definition
Defect: Fructokinase, autosomal recessive
Benign, asymptomatic
Fructose in blood and urine |
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Term
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Definition
Defect: Aldolase B, autosomal recessive
F-1-P accumulates, causing a dec in available phosphate
Results in inhibition of glycogenolysis and gluconeogenesis
Hypoglycemia, jaundice, cirrhosis and vomiting
Tx: Dec intake of fructose AND sucrose |
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Term
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Definition
Galactitol accumulates if galactose is present in diet
Mild, autosomal recessive
Galactose in blood and urine, infantile cataracts
Failure to track objects or social smile |
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Term
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Definition
Galactose-1-phosphate uridyltransferase, AR
Damage from accumulation of toxic substances
FTT, jaundice, hepatomegaly, infantile cataracts, MR,
Tx: exclude galactose and lactose from diet |
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Term
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Definition
Alternative to trapping glucose in cells is to convert it to sorbitol via *Aldolase Reductase
Can also confer sorbitol to fructose via *Sorbitol dehydrogenase
Cataracts, retinopathy, peripheral neuropathy |
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Term
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Definition
| Hereditary lactose intolerance due to loss of brush border enzymes |
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Term
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Definition
Essential- Met, Val, His (gluc) Ile, Phe, Thr, Trp (both) Leu, Lys (Keto)
Acidic- Asp and Glu
Basic- Arg, Lys, His |
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Term
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Definition
RLE: CPS1 NH4 > Carbamoyl phosphate
Ornithine, Carbamoyl Phosphate, Citrulline, Aspartate, Arginosuccinate, Fumarate, Arginine, Urea
Ornithine transcarbamoylase and RLE are only two in the mitochondria |
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Term
| Alanine and Glutamate transport |
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Definition
| Amino acids > Glutamate > Alanine > Glutamate > Urea |
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Term
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Definition
Acquired or hereditary
Results in excess NH4, which depletes a-KG, leading to inhibition of TCA cycle
Tremor, slurring speech, somnolence, vomiting, cerebral edema, blurring vision
Tx- limit protein, Use benzoate or phenylbutyrate, Lactulose |
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Term
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Definition
X linked, body can't eliminate ammonia
Often evident in the first few days of life, may present with late onset
Excess carbamoyl phosphate is converted to orotic acid
Inc orotic acid in blood and urine, Dec BUN, hyperammonemia |
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Term
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Definition
Tyrosine (thyroxine) > Dopa > DA > NE > Epi
Needs BH4, B6 and Vit C |
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Term
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Definition
Niacin > NAD (needs B6)
Serotonin > Melatonin (needs BH4) |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
Phe > Tyr (Phe hydroylase)
Tyr > Dopa (Try hydroxylase)
Dopa > DA (Dopa decarboxylase)
DA > NE (DA B-hydroxylase)
NE > Epi (Phenylethanolamine N-methyltransferase) |
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Term
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Definition
Dec Phenylalanine hydroxylase deficiency or THB deficiency
Tyrosine becomes essential
MR, growth retardation, seizures, fair skin, eczema, musty odor
Inc tyrosine in diet, dec Phe |
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Term
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Definition
Lack of proper dietary therapy during pregnancy
In infnant: microcephaly, MR, growth retardation, congenital heart defects |
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Term
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Definition
Def in homogentisic acid oxidase in the degredative pathways of tyrosine fumarate
Dark connective tissue, brown pigmented sclera, urine turns black after long exposure, arthralgias |
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Term
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Definition
Deficiency of either:
Tyrosinase - can't synthesize melanin from tyrosine
Defective tyrosine transporters
Lack of migration of NC cells
Lack of melanin leads to inc risk of skin cancer |
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Term
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Definition
Cystathione synthase def - tx: Dec Met, Inc cys, and inc B12 and folate in diet
Dec affinity of cystathione synthase for pyridoxal phosphate - tx inc B6
Homocysteine methyltransferase (req B12) deficiency
MR, osteoporosis, tall stature, kyphosis, lens subluxation, atherosclerosis |
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Term
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Definition
Hereditary defect of renal tubular amino acid transporter for cysteine, ortnithine, lysine and arginine in the PCT ("COLA")
Precipitation of hexagonal crystals and renal stag horn calculi
Tx: Good hydration and urinary alkalization |
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Term
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Definition
a-KG deficiency
Blocked degradation of branched amino acids (Ile, Leu, Val)
CNS defects, MR, death
"I love vermont maple syrup" |
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Term
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Definition
Defective neutral amino acid transporters on renal and interstitial epithelial cells (like cystinuria)
Causes tryptophan excretion in urine and dec absorb in gut
Leads to pellagra (Dermatitis, diarrhea, dementia, death) |
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Term
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Definition
Epi and glucagon stimulate glycogenolysis
Insulin stops glycogenolysis |
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Term
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Definition
Branches have 1,6 bonds; linkages have 1,4 bonds
Sk Mm: G1P > G6P which is rapidly metabolized
Hepatocytes: stored and undergoes glycogenolysis to maintain blood sugar
G6P > G1P > UDP-glucose > chains |
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Term
| Enzymes in Glycogenolysis |
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Definition
Glycogen synthase (RLE) 1,4 links
Branching enzyme- 1,6 links |
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Term
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Definition
G6P deficiency
Severe fasting hypoglycemia, Inc glycogen in liver, Inc blood lactate, hepatomegaly
Autosomal recessive |
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Term
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Definition
Lysosomal a-1,4-glucosidase
Cardiomegaly, systemic findings > early death
AR "trashes the pump" |
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Term
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Definition
Debranching enzyme (a-1,6-glucosidase)
Milder form of type 1 with normal blood lactate levels
AR, gluconeogenesis is intact |
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Term
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Definition
Sk Mm glycogen phosphorylase
Inc glycogen in muscle, painful Mm cramps, myoglobinuria |
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Term
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Definition
a-galactosidase A deficiency
Accumulated: Ceramide trihexidose
Peripheral neuropathy, angiokeratomas, CV/renal dz
*XR
"Fabricate the ceramics gala, eh" |
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Term
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Definition
Glucocerebrosidase deficiency
Accumulated: Glucocererbroside
Most common, Hepatosplenomegaly, aseptic necrosis of femur
*crumpled tissue paper cells |
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Term
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Definition
Sphingomyelinase
Acc: Sphingomyelin
neurodegeneration, hepatosplenomegaly, cherry red spot on macula, foam cells
"Pick your brain with your sphinger" |
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Term
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Definition
Hexosaminidase A
Acc: GM2 ganglioside
Neurodegeneration, cherry red spot on macula, lysosomes with onion skin,
*NO hepatosplenomegaly
"Hex the jew at GM" |
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Term
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Definition
Galactocerebrosidase
Acc: galactocerebrosidase
Peripheral neuropathy, MR, globoid cells |
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Term
| Metachromatic leukodystrophy |
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Definition
Arylsulfatase
Acc: cerebroside sulfate
Central and peripheral demyelination with ataxia and dementia |
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Term
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Definition
a-L-iduronidase def
Acc: Heparan and dermatan sulfate
Garoylism, airway obstruction, corneal clouding, hepatosplenomegaly, MR |
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Term
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Definition
Iduronate sulfatase
Acc: Heparan and dermatan sulfate
Mild hurlers with aggressive behavior
*no corneal clouding
XR |
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Term
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Definition
Inability to transport LCFAs into the mitochondria, resulting in toxic accumulation
Weakness, hypotonia, hypoketotic hypoglycemia |
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Term
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Definition
In the liver, FA and AA are metabolize to acetoacetate and B hydroxybutyrate
OAA is depleted for energy in starving state |
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Term
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Definition
Glycolysis and aerobic respiration
Insulin stim storage of lipids, proteins and glycogen |
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Term
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Definition
| Hepatic glygenolysis, gluconeogenesis, adipose release FFA |
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Term
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Definition
Glucose maintained by hepatic glycogenolysis, adipose release of FFA, hepatic gluconeogensis from tissue lactate and alanine
RBCs cannot use ketones |
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Term
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Definition
| Adipose stores, protein degredation |
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Term
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Definition
RLE is HMG CoA reductase
Statins block this |
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Term
| Lipid transport, key enzymes |
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Definition
LCAT - catalyze esterification of cholesterol
CEPT- mediates transfer of cholesterol esters to other lipoprotein particles |
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Term
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Definition
Mediates remnant uptake
On every type |
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Term
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Definition
Activates LCAT
On HDL, maybe CM |
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Term
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Definition
LPL cofactor
On CM, VLDL and HDL |
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Term
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Definition
CM secretion
On CM and CM remnant |
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Term
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Definition
Binds LDL receptor
On VLDL, IDL and LDL |
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Term
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Definition
Delivers dietary TGs to peripheral tissues
Cholesterol to liver in form of remnant
Secreted by intestinal epithelial cells |
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Term
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Definition
Hepatic TGs to peripheral tissues
Liver |
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Term
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Definition
| Delivers TGs and cholesterol to liver |
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Term
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Definition
| Delivers hepatic cholesterol to peripheral tissues |
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Term
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Definition
Mediates reverse cholesterol transport from periphery to liver
Secreted by both liver and intestine |
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Term
| Hyper chylomicronemia (1) |
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Definition
LPL deficiency or altered Apo C2
Inc CM, TG, cholesterol
pancreatitis, hepatosplenomegaly, eruptive xanthomas |
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Term
| Familia hypercholesterolemia (2) |
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Definition
Absent LDL R
Inc, LDL, cholesterol
Accelerated atherosclerosis, tendon xanthomas, corneal arcus |
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Term
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Definition
hepatic over production of VLDL
Inc VLDL and TG
Pancreatitis |
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Term
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Definition
AR in MTP gene
Dec B-48 and B100
Dec CM and VLDL synthesis and secretion
Lipid accumulation in enterocytes
FTT, steattorrhea, acantholysis, ataxia, night blindness |
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