Exam 4 purines, pyrimidines and porphyrins section: things to know

Question 1

Lesch-Nyhan Syndrom

Answer 1

self-mutilating behavior;hyperuricemia; uric acid in urine; low HGPRT activity.

Hyperuricemia caused by decreased purine reutilization.
HGPRT is used to recycle purines

Question 2

methotrexate

Answer 2

folic acid analog; can cause folic acid deficiency; symptoms of weakeness, fatigability, nausea and diarrhea

Question 3

what do you make from inosine

Answer 3

purines, pyrimydines, GMP from XMP

you need inosine to make pyrimidines to make CTP from UTP

Question 4

what inhibits PRPP in purine synthesis?

Answer 4

AMP, IMP, GMP

Question 5

what inhibits phosphoribosylamine? in purine synth.

Answer 5

AMP, IMP, GMP

Question 6

purine synt: what inhibits IMP dehydrogenase

Answer 6

GMP

Question 7

purine synt: what inhibits adenylosuccinate synthetase?

Answer 7

AMP

Question 8

what activates ribonucleotide reductase? what inhibits it ?

Answer 8

ATP; inhibited by dATP

Question 9

crigler-najjar syndrome, type I

Answer 9

jaundice; increased unconjugated bilirubin level in serum, low fecal urobilinogen level; liver biopsy result low activity of enzyme UDP-glucoronyl transferase.

Question 10

gilbert syndrome

Answer 10

jaundice, decreased UDPGT activity. no history of dark colored urine, clay colored stools, abdominal, blood transfusion, illegal drug use. no alcohol compsumption.
high unconjugated bilirubin without other symptoms

Question 11

porphyria cutanea tarda

Answer 11

chronic blistering and scarring of skin when exposed to sunlight; smoker, drinker, worsen his condition. urine and plasma havehigh level of uroporphyrin.
uroporphyrinogen decarboxylase deficiency.

Question 12

acute intermittent porphyria

Answer 12

treat with glucose; intravenous hemin injection to decrease synthesis of hepatic ALAS1.
NOT photosensitive. PBG deaminase defect. PBG and ALA accumulate in urine.
abdominal pain, motor system neuropathies, induced by drugs, alcohol and sun exphsure.

Question 13

regulation of heme synthesis

Answer 13

ALA synthase is rate-limiting. regulated by loevels of heme. inhibit expression of ALAS1, transfer of ALAS1 to mito, catalytic activity of ALAS1.

Question 14

erythropoeitic protoporphyria

Answer 14

deficiency in ferrochetalase

Question 15

role of ferrochelatase

Answer 15

needs ascorbic acid and cysteine. converts protoporphyrin IX into protoheme IX

Question 16

neonatal jaundice

Answer 16

low level lingandin in liver at birth
low hepatic glucuronyl-transferase activity
treat with phototherapy or exchange transfusion
light from fluorescent lamp

Question 17

Gout

Answer 17

pain in big toe, joint pain, alcohol and beef consumption. sodium urate has reduced solubility at lower temperature.

Question 18

primary renal and primary metabolic gout

Answer 18

renal: hyperuricemia caused by underexcretion of uric acid
metabolic: over production of purines and uric acid

Question 19

committed step in biosynthesis of adenine and guanine nucleoside monophosphates is catalyzed by

Answer 19

glutamine-PRPP amidotransferase; inhibited by AMP, GMP and IMP; activated by PRPP

Question 20

allopurinol

Answer 20

inhibits xanthine oxidase

Question 21

pyrimidine nucleotide biosynthesis regulated by allosteric binding of UTP to

Answer 21

ribose 5 phosphate as a substrate

Question 22

folate deficiency leads to decreased rate of synthesis of

Answer 22

amino acids, thymidylate and AMP

Question 23

lead intoxication mechanism

Answer 23

inhibition of enzymes in her RBCs that are present in the mito and in the cytosol. affects ALA dehydratase and ferrochelatase

Question 24

in porphyria cutanea tarda, phlebotomy is used form

Answer 24

reducing iron stores since can be influenced by hepatic iron overload

Question 25

crigler-Najjar syndrome type II

Answer 25

presence of bilirubin monoglucuronide conjugates in urine. UDPGT deficiency is benign. partial deficiency of gene.

Question 26

ALA synthase reaction

Answer 26

glycine to delta-aminolevulinate with pyridoxal phosphate

Question 27

bilirubin formation

Answer 27

hemoglobin to heme, heme to biliverdin, beliverdin to bilirubin

Question 28

what does biliary obstruction cause?

Answer 28

elevated direct/conjugated bilirubin in blood: if blilirubin is conjugated, UDPGT works, so there no deficit, which causes CN I and II and Gilbert syndrom

Question 29

mechanism of methotrexate

Answer 29

inhibits dihydrofolate reductase to suppress synthesis of dTMP and purine nucleotides. antiinflammatory used for RA.

Question 30

why is folate important in treating pernicious anemia?

Answer 30

tetrahydrofolate derivatives are essential for the synthesis of IMP and dTMP in humans.

Question 31

febuxostat mechanism

Answer 31

xanthine oxidase inhibitor

Question 32

colchicine

Answer 32

inhibit microtubule formation and prevents phagocytic cells from engulfing urate crystals. used for gout to alleviate inflammation.

Question 33

uricosuric agents

Answer 33

promote renal clearance of uric acid by inhibiting a urate-anion exchanges that mediates urate re-absorption.

Question 34

how does 5-flurouracil (5-FU) treatment work?

Answer 34

suppresses cell prolieration by inhibiting dTMP (thymidylate) synthesis

Question 35

Adenosine deaminase deficiency

Answer 35

causes immune dysfunction due to accumulation of dATP in body, which is a potent inhibitor of ribonucleotide reductase. treat with bone marryow transplant.

Question 36

chronic hepatitis symptoms

Answer 36

jaundice, mildly protruberant abdomen, high serum levels of indirect bilirubim. disease impairs bilirubin conjugation and thus increases level of unconjugated bilirubin in blood

Question 37

excess unconjugated bilirubin

Answer 37

increased bilirubin formation defective liver uptake defective conjugation

Question 38

excess conjugated bilirubin

Answer 38

defective transport to bile | bile duct blockage

Question 39

what is secreted along with urobilinogens that are not absorbed

Answer 39

stercobilin, orange browned colored pigments

Question 40

ALA dehydratase reaction

Answer 40

ALA to PBG; needs zinc; inhibited by lead, can cause anemia and lead poisoning

Question 41

hemolytic anemia

Answer 41

anemia, enlarged spleen, jaundice, blood problem; bizarre looking RBCs, pyruvate kinase deficiency. disease involved excess bilirubin load because can't metabolize bilirubin or because of hemolytic process. breakdown of RBCs causes hemolytic jaundice. increased indirect plasma biliruben. increased urobilonogen level in plasma and urine.

Question 42

how does body compensate in pyruvate kinase deficiency?

Answer 42

increase 2,3BPG

Question 43

three types of hyperbilirubinemia

Answer 43

hemolytic anemia: high un/con bili (bile) hepatitis: high un/con blood) biliary duct stone: hih unco blood/high con blood

Question 44

why use phenobarbital to treat Crigler-Najjar syndrome type II?

Answer 44

phenobarbital can induce synthesis of hepatic UDP glucuronyl transferase (UDPGT) so that bilirubin conjugation can be stimulated in the patient. won't work for type I.

Question 45

Dubin Johnson syndrome

Answer 45

jaundice no enlarged liver or spleen, no liver failure; abnormally elevated levels of conjugated bilirubin and several liver enzyumes. high coproporphyrin I and III in urine. liver was dark green. caused by defective transporter for conjugated bilirubin.

Question 46

what causes porphyria cutanea tarda

Answer 46

deficiency in urophorpyrinogen decarboxylase. uroporphyrin accumulates in urine and patients are photosensitive.