Exam 4 purines, pyrimidines and porphyrins section: things to know Flashcards
Lesch-Nyhan Syndrom
self-mutilating behavior;hyperuricemia; uric acid in urine; low HGPRT activity.
Hyperuricemia caused by decreased purine reutilization.
HGPRT is used to recycle purines
methotrexate
folic acid analog; can cause folic acid deficiency; symptoms of weakeness, fatigability, nausea and diarrhea
what do you make from inosine
purines, pyrimydines, GMP from XMP
you need inosine to make pyrimidines to make CTP from UTP
what inhibits PRPP in purine synthesis?
AMP, IMP, GMP
what inhibits phosphoribosylamine? in purine synth.
AMP, IMP, GMP
purine synt: what inhibits IMP dehydrogenase
GMP
purine synt: what inhibits adenylosuccinate synthetase?
AMP
what activates ribonucleotide reductase? what inhibits it ?
ATP; inhibited by dATP
crigler-najjar syndrome, type I
jaundice; increased unconjugated bilirubin level in serum, low fecal urobilinogen level; liver biopsy result low activity of enzyme UDP-glucoronyl transferase.
gilbert syndrome
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
porphyria cutanea tarda
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.
acute intermittent porphyria
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.
regulation of heme synthesis
ALA synthase is rate-limiting. regulated by loevels of heme. inhibit expression of ALAS1, transfer of ALAS1 to mito, catalytic activity of ALAS1.
erythropoeitic protoporphyria
deficiency in ferrochetalase
role of ferrochelatase
needs ascorbic acid and cysteine. converts protoporphyrin IX into protoheme IX
neonatal jaundice
low level lingandin in liver at birth
low hepatic glucuronyl-transferase activity
treat with phototherapy or exchange transfusion
light from fluorescent lamp
Gout
pain in big toe, joint pain, alcohol and beef consumption. sodium urate has reduced solubility at lower temperature.
primary renal and primary metabolic gout
renal: hyperuricemia caused by underexcretion of uric acid
metabolic: over production of purines and uric acid
committed step in biosynthesis of adenine and guanine nucleoside monophosphates is catalyzed by
glutamine-PRPP amidotransferase; inhibited by AMP, GMP and IMP; activated by PRPP
allopurinol
inhibits xanthine oxidase
pyrimidine nucleotide biosynthesis regulated by allosteric binding of UTP to
ribose 5 phosphate as a substrate
folate deficiency leads to decreased rate of synthesis of
amino acids, thymidylate and AMP
lead intoxication mechanism
inhibition of enzymes in her RBCs that are present in the mito and in the cytosol. affects ALA dehydratase and ferrochelatase
in porphyria cutanea tarda, phlebotomy is used form
reducing iron stores since can be influenced by hepatic iron overload
crigler-Najjar syndrome type II
presence of bilirubin monoglucuronide conjugates in urine. UDPGT deficiency is benign. partial deficiency of gene.
ALA synthase reaction
glycine to delta-aminolevulinate with pyridoxal phosphate
bilirubin formation
hemoglobin to heme, heme to biliverdin, beliverdin to bilirubin
what does biliary obstruction cause?
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
mechanism of methotrexate
inhibits dihydrofolate reductase to suppress synthesis of dTMP and purine nucleotides. antiinflammatory used for RA.
why is folate important in treating pernicious anemia?
tetrahydrofolate derivatives are essential for the synthesis of IMP and dTMP in humans.
febuxostat mechanism
xanthine oxidase inhibitor
colchicine
inhibit microtubule formation and prevents phagocytic cells from engulfing urate crystals. used for gout to alleviate inflammation.
uricosuric agents
promote renal clearance of uric acid by inhibiting a urate-anion exchanges that mediates urate re-absorption.
how does 5-flurouracil (5-FU) treatment work?
suppresses cell prolieration by inhibiting dTMP (thymidylate) synthesis
Adenosine deaminase deficiency
causes immune dysfunction due to accumulation of dATP in body, which is a potent inhibitor of ribonucleotide reductase. treat with bone marryow transplant.
chronic hepatitis symptoms
jaundice, mildly protruberant abdomen, high serum levels of indirect bilirubim. disease impairs bilirubin conjugation and thus increases level of unconjugated bilirubin in blood
excess unconjugated bilirubin
increased bilirubin formation
defective liver uptake
defective conjugation
excess conjugated bilirubin
defective transport to bile
bile duct blockage
what is secreted along with urobilinogens that are not absorbed
stercobilin, orange browned colored pigments
ALA dehydratase reaction
ALA to PBG; needs zinc; inhibited by lead, can cause anemia and lead poisoning
hemolytic anemia
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.
how does body compensate in pyruvate kinase deficiency?
increase 2,3BPG
three types of hyperbilirubinemia
hemolytic anemia: high un/con bili (bile)
hepatitis: high un/con blood)
biliary duct stone: hih unco blood/high con blood
why use phenobarbital to treat Crigler-Najjar syndrome type II?
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.
Dubin Johnson syndrome
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.
what causes porphyria cutanea tarda
deficiency in urophorpyrinogen decarboxylase. uroporphyrin accumulates in urine and patients are photosensitive.
