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B800 - Unit 3
disease, dugs, etc.
75
Biochemistry
Graduate
11/01/2013

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Term
fluorouracil
Definition
suicide inhibitor; irreversible inhibition of thmidylate synthase; chemotherapy agent
Term
hydroxyurea
Definition
sickle cell reduces rate of attacks; decreases deoxyribonucleotide production via inhibition of ribonucleotide reductase
Term
methotrexate
Definition
competitively inhibits dihydrofolate reductase; inhibits synthesis of DNA, RNA, thymidylates, and proteins; cancer, immune, and eptopic pregnancy treatment
Term
gemcitabine
Definition
competitive inhibitor incorporated into cytidine; arrests tumor growth by stopping DNA synthesis early and signaling apoptosis
Term
acyclovir
Definition
antiviral drug; treats herpes; competitive inhibitor of guanosine kinase in viruses; further activated by the phosphorylation of the viral enzyme; inhibits DNA polymerase and synthesis
Term
DDI
Definition
antiretroviral; reverse transcriptase inhibitor; treats HIV; nucleoside analogue of guanosine; chain termination and inhibits complementary DNA enzyme (reverse transcriptase)
Term
DDC
Definition
pyrimidine analong; reverse transcriptase inhibitor; phosphorylated in T cells and other HIV target cells into its active form; only effective against retroviruses
Term
AZT
Definition
reverse transcriptase inhibitor; azide group allows it to cross BBB
Term
azathioprine
Definition
immunosuppressve; activated to methyl-thioinsine monophosphate by cellular enzymes; blocks purine synthesis especially effective in DNA synthesis inhibition in T and B cell lymphocytes
Term
6-mercaptopurine
Definition
immunosuppressive; acts early in purine synthesis to compete with guanine and hypozanthine at the IMP step (AMP or GMP pathway commitment step)
Term
allopurinol
Definition
xanthine oxidase inhibitor; increases exretion of more soluble xanthine or hypoxanthine
Term
febuxostat
Definition
xanthine oxidase inhibitor; increases exretion of more soluble xanthine or hypoxanthine
Term
probenecid
Definition
inhibition of renal urate re-absorption; treatment for hyperuricemia
Term
rasburicase
Definition
converts uric acid to allantoin; recombinant uricase; limited to treatment of tumor lysis syndrome induced hyperuricemia
Term
acute intermittent porphyria (AIP)
Definition
defect in porphobilinogen deaminase
PBG accumulates
increased demand for heme in liver activates the deficiency symptoms
treated with hemin infusion
Term
porphyria cutanea tarda (PCT)
Definition
defect in uroporphyrinogen decarboxylase
uroporphyrinogen III and I accumulate
acquired deficiency
activated by alcohol abuse and hepatitis C
treated with phlebotomy and reduction of hepatic iron
Term
ribonucleotide reductase
Definition
catalyzes reduction of ribose moiety (ADP, GDP, and CDP) to deoxyribose
part of purine de novo synthesis
only works on diphosphate form
adds hydrogen and releases water
Term
purine parts
Definition
glycine - base
C8 - methyl-FH4
N3 - glutamine
C6 - CO2
N1 - aspartate
C2 - formyl-FH4
Term
pyrimidine parts
Definition
base - aspartate
N3 - glutamine
C2 - CO2
Term
Thymidylate synthase
Definition
dUMP + n5n10-methylene-tetrahydrofalte --> dTMP + dihydrofolate
Term
purine synthesis regulation
Definition
(+) PRPP,
(-) IMP, GMP, AMP, mycophenolic acid
Term
FIAU
Definition
inhibits mitochondrial DNA and enzymes
causes lactic acidosis and liver failure
blocks gluconeogenesis, blocks FOX, decreased oxidation of lactate
Term
Lesch-Nyhan syndrome
Definition
Cause: deficiency of HGPRT, X-linked
S/S: failure of purine salvage, hyperuricemia, self-mutilation, mental retardation
Term
Adenosine deaminase deficiency
Definition
Blocks iodine from adenosine reaction
Increased levels of adenosine blocks nucleotide synthesis
Affects immune cell proliferation immensely, causes immunodeficiency
Term
Acute intermittent porphyria
Definition
Defect in pohobilinogen deaminase
Porphobilinogen accumulates
Occurs when there is increased demand for home synthesis
Treat with hemin infusion
Term
Porphyria cutanea tarda
Definition
Defect in uroporphyrinogen decarboxylase
Uroporphyrinogen III and I accumulate
Activated by alcohol abuse and hepatitis C
Treat with phlebotomy and hepatic iron reduction
Term
ALA dehygrogenase deficiency
Definition
Associated with lead poisoning
Term
Eryhtropoietic protophyria
Definition
Associated with lead poisonong
Term
7-a-hydroxylase
Definition
Converts cholesterol to 7-hydroxycholesterol
First step in bile salt synthesis, rate-limiting step
(+) low intracellular [bile salt]
(-) high intracellular [bile salt]
Term
ABCB11
Definition
Active transported of bile from hepatocyte to bile duct
Term
SLC10A2
Definition
Sodium-linked transporter in distal ileum
Intestine lumen to intestinal cell to portal blood
Term
SLC10A1
Definition
Sodium-linked transporter in liver
Transports bile from portal blood into hepatocyte
Term
Increased indirect bilirubin
Definition
Hemolysis, increased production
Heart failure, impaired uptake
C-N or Gilbert, impaired conjugation ability
Term
Increased direct bilirubin
Definition
Appears in urine
Liver or bile duct disease, impaired excretion
Both indirect and direct high in blood
Term
Gilbert syndrome
Definition
decreased UDP-gluconyltransferase activity due to promoter mitatiom
stress worsens, result in jaundice and increased indirect bilirubin blood level
Term
Crigler Najjar syndrome
Definition
Inactive UDP-gluconyltransferase due to coding region mutation
Increased levels of unconjugated bilirubin
Term
Dubin-Johnson syndrome
Definition
cMOAT (transporter) is defective, less transport of bilirubin into bile
Aka ABCC2, MRP2
Increased levels of conjugated bilirubin
Term
Polyol pathway
Definition
Glc + NADPH --> sorbital + NADP+
Enzyme: aldose reductase
Increased pathway use with increased blood glucose
Sorbitol has osmotic effects in eyes, causes eye symptoms of DM
Term
Glyoxylase system
Definition
Increased activity with increased blood glucose levels
Gets rid of methylgluoxal which is dangerous but makes lactate
Term
Hexosamine pathway
Definition
Increased activity with increased blood glucose levels
Alters glycosylation of proteins and lipids
Alters transcription activity
Might cause insulin resistance
Term
Advanced glycation end products
Definition
Increased amounts with increased blood glucose levels
Ex: Schiff base, global, methylgloxal, fructosamine
Believed to cause blood vessel issues of DM
Very reactive and potentially damaging molecules
Term
MODY
Definition
Maturity onset diabetes of the young
Monogeneticndisease, i.e. mutation in glucokinase, TFs, MODY X
Single gene mutation that results in DM
Term
Hepatic steatosis
Definition
S/s: enlarged liver, high ALT and AST, bright liver on ultrasound, far globules on liver biopsy
Causes: alcoholic and non-alcoholic (obesity, DM2, metabolic syndrome)
Term
ALD vs. NAFLD
By ANI
Definition
ANI <0 --> NAFLD
ANI >0 --> ALD
ANI = -58.5 + 0.637(MCV) + 9.31(AST/ALT) - 0.406(BMI) + 6.35(MALE)
Term
Metabolic syndrome
Definition
Characteristics: central waist circumference obesity, dyslipidemia (TAG high, HDL low), high fasting blood glucose
Term
Safe alcohol consumption
Definition
Male: 40-60g/day; 2-3 drinks
Female: 10-20g/day; 1 drink
12-14g = 12oz beer, 4oz wine, 1.5oz spirits
Term
pO2 per Hb saturation
Definition
40-50-60 to 70-80-90
40mmHg to 70% saturation
50 to 80%
60 to 90%
170 to 99%
Term
Methemoglobin
Definition
Fe is oxidixed to 3+ state, cannot bind O2
Oxygen content and delivery are reduced without cardiac output signaled to increase
Pulse oximeter plateaus at 85%
Chocolate blood
Caused by drugs and oxidant stress
Term
Microsomal p450s
Definition
Localized to ER
Use oxygen in intermediary to metabolize drugs
Term
Mitochondrial p450s
Definition
Localized to inner mitochondrial membrane (mostly in adrenal glands and gonads)
Use oxygen for synthetic reactions (steroids, bile salts, etc.)
Term
General p450 reaction
Definition
Iron(III) in p450 binds substrate
Iron is reduced (to II)
Oxygen is added to complex
Oxygen is changed to reactive form
Results in hydroxylation of substrate
Term
ROS synthetic processes/enzymes
Definition
NADH/NADPH oxidase, xanthine oxidase, lipoxygenase, cyclooxygenase, p450 monooxygenase, mitochondrial oxidative-phosphorylation, superoxide dismutase, Fenton reaction
Term
Major ROS groups
Definition
Superoxide O2•-
Hydrogen peroxide H2O2
Hydroxyl radical OH•-
Term
Sulfonylureas & meglitinides
Definition
Anti-diabetic drug
Stimulate insulin release by B cells
Target SUR1 subunit of K+ channel
Closes K+ channel, depolarizes B cell, opens Ca2+ channels, signals insulin secretion
Adverse: hypoglycemia, weight gain
Term
Glucosidase inhibitors
Definition
Anti-diabetic drug
Inhibit intestinal a-gluconidase
Reduce glucose formation from ingested polysaccharides
Adverse: flatulence, abdominal discomfort
Term
Thiazolidinediones
Definition
Anti-diabetic drug, insulin sensitizers
Targets PPAR-gamma, increases FA uptake, decrease lipolysis, increase insulin sensitizing factors, decrease insulin resistance factors
Adverse: weight gain
Term
Pramlintide
Definition
Anti-diabetic drug, variant of skyline of B cell
Suppresses glucagon secretion, suppresses insulin secretion, delays gastric emptying, decrease appetite and weight
Term
Glp-1 drugs
Definition
Anti-diabetic drugs
Homolog of natural Gulp-1
Increase insulin secretion in glucose-dependent manner, decrease glucagon secretion, increase insulin sensitivity, increase B cell mass and expression of insulin gene, delays gastric emptying, increase brain satiety
Ex: Exenatide, Liraglutide, CJC-1131, Albugon
Term
Enterocyte metabolism of glutamine
Definition
Glutamine --> alanine + NH4+ + CO2 + energy
Term
Lymphoblast metabolism of glutamine
Definition
Glutamine --> NH4+ + aspartate + energy
Term
periportal hepatocyte
Definition
takes up glutamine and some ammonium
excretes urea
Term
Perivenous hepatocyte
Definition
Capture ammonium missed by periportal cells and fix it into Glutamine using Glutamine synthetase
Term
70 kg man fuel
Definition
70g liver glycogen
120g muscle glycogen
20g circulating glucose
15kg adipose fat
6kg muscle protein
Term
Glycogen synthase
Definition
Adds glucose residues to growing glycogen (a-1,4)
(-) phosphorylation
(+) G6P, dephosphorylation
Term
Glycogen phosporylase
Definition
(-) dephosphorylation
(+) phosphorylation
Term
PFK2
Definition
Fasted = phosphatase form, phosphorylated
Fed = kinase form, dephosphorylated
Term
Pyruvate dehydrogenase
Definition
(-) phosphorylation, acetyl CoA (indirect)
(+) dephosphorylation
Term
Acetyl-CoA carboxylase
Definition
(-) phosphorylation
(+) dephosphorylation, citrate, insulin
Term
Pyruvate kinase
Definition
(-) phosphorylation
(+) dephosphorylayion, F-1,6,-bP, acetyl CoA
Term
Malonyl CoA decarboxylase
Definition
Converts malynyl CoA back to acetyl CoA in muscles, allows FA oxidation to proceed
(-) dephosphorylation
(+) phosphorylation
Term
G6PDH deficiency
Definition
X-linked recessive
Exacerbated by oxidant drugs, antimalarial compounds, hepatitis a/infections, and diet
Presents with weakness, fatigue, yellowing, fever, elevated indirect bilirubin, low Hb, low hematocrit, heinz bodies, hemoglobinuria
Term
Lactose intolerance
Definition
Abdominal pain, flatulence, diarrhea, and naseau with lactose exposure
Compromised lactase activity
Term
Galactosemia
Definition
Defect of galactose-1-phosphate uridyltransferase (GALT)
Feeding difficulty, vomiting, jaundice, hepatomegaly, hypoglycemia, CATARACTS
Term
Hereditary fructose intolerance
Definition
Defect in aldolase B
Hypoglycemia, fructosemia, fructosuria, hyperuricemia, lactic acidosis, urine with reducing sugar, urine negative for glucose
Term
Essential fructosuria
Definition
Lack of fructokinase A
means unable to convert fructose to phosphate form
Symptoms due to kidney elimination of fructose
Similar to aldolase B deficiency
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