Purine and Pyrimidine Metabolism Flashcards
What are the oxidation levels of adenine, guanine, hypoxanthine, xanthine, and uric acid?
Adenine = 0
Guanine/Hypoxanthine = 1
Xanthine = 2
Uric acid = 3
Explain PRPP synthetase…
Ribose-5-phosphate –> PRPP (purine synthesis)
What step is the committed step in purine synthesis?
PRPP –> PRA
Which step has the addition of THF in purine synthesis?
PRA –> IMP
Explain ribonucleotide reductase…
RNA –> DNA
Explain carbamoyl phosphate synthetase II…
Gln –> carbamoyl phosphate (pyrimidine synthesis)
*Committed step
Explain aspartate transcarbamoylase (ATCase)…
Carbamoyl phosphate –> carbamoyl aspartate
Explain UMP synthase…
Orotate + PRPP –> OMP
OMP –> UMP
What Dx is associated with defects in UMP synthase?
Orotic aciduria
Which step has the addition of THF in pyrimidine synthesis?
dUMP –> dTMP
What enzyme is targeted to prevent graft rejection by depriving cells of GMP/dGTP? How does it work?
IMP dehydrogenase…prevents IMP –> XMP which prevents GMP synthesis and inhibits DNA replication of B and T cells
How do Sulfa Drugs work?
Antibacterial that competitively inhibits the enzyme that adds PABA to folate, therefore inhibiting DNA replication in cancer cells
Explain AMP deaminase…
AMP –> IMP (purine catabolism)
Explain adenosine deaminase (ADA)
Adenosine –> Inosine (purine catabolism)
What are the Dx’s associated with ADA defects?
Increased ADA –> hemolytic anemia
Decreased ADA –> SCID
What is SCID?
“Bubble Boys”
Defect in ADA –> increased adenosine
Adenosine –> dATP which inhibits ribonucleotide reductase, thus inhibiting DNA synthesis of B and T cells
Explain xanthine oxidase…
Hypoxanthine –> xanthine (purine catabolism)
Xanthine –> Uric acid (purine catabolism)
What drug is used to inhibit xanthine oxidase and what Dx does it relieve?
Allopurinol…relieves Gout
What Dx is associated with increased uric acid production?
Gout
Explain uridine phosphorylase…
Deoxyuridine/Uridine –> uracil (pyrimidine catabolism)
Deoxythymidine –> thymine (pyrimidine catabolism)
Explain APRT…
Adenine + PRPP –> AMP (purine salvage pathway)
Explain HGPRT…
Guanine/Hypoxanthine + PRPP –> GMP/IMP (purine salvage pathway)
What Dx is associated with defects in HGPRT?
Increased uric acid (Lesch-Nyhan syndrome)
Explain uridine phosphorylase…
Uracil –> uridine (pyrimidine salvage)
Explain uridine kinase…
Uridine –> UMP (pyrimidine salvage)
Explain thymidine phosphorylase…
thymine –> deoxythymidine (pyrimidine salvage)
Explain thymidine kinase…
Deoxythimidine –> dDMP (pyrimidine salvage)
What are the 2 Dx that cause Gout and what kind of diet triggers gout?
Primary hyperuricemia - over production of uric acid
Secondary hyperuricemia - under excretion of uric acid
Diet - high in meat, seafood, beer
What is Lesch-Nyhan syndrome?
Defect in HGPRT leading to primary hyperuricemia.
PRPP not used in salvage pathway so used for purine synthesis leading to retardation and self-mutilation
What is Acyclovir used for?
Antiviral that resembles guanine.
Incorporated into viral DNA to inhibit DNA replication
