Nucleotide Metabolism Flashcards
What molecules are purines?
Adenosine, and Guanine
Pur As Gold
what reaction does UMP synthase catalyze?
Orate –> UMP
What vitamin does methotrexate compete w/?
folate (B9)
what does uridine phosphorylase do?
catalyzes Uracil –> uridine
in pyrimidine salvage
What is the rate limiting step and enzyme in purine synthesis?
PRPP —->PRA
through GPPA
What is the very basic sequence of purine synthesis?
Sugar made, add base
What is the rate limiting reaction and enzyme in pyrimidine synthesis?
Carbamoyl phosphate –> carbamoyl aspartate
enzyme: aspartate transcarbamoylase
What molecules are pyrimidines?
Cytosine, Uracil, Thymine
CUT the Py
What is the very basic sequence of pyrimidine synthesis?
Make base first, then add sugar
think this because the base is 1 ring, simple, so it’s made first
What is the basic path of uracil salvage (pyrimidine)?
Uracil –uridine phosphorylase–> uridine –>–>–> UTP
What is gout?
overproduction of uric acid usually because of diet high in purines/red meat; sodium urate turns into crystals that are painful and accumulate in toes and fingers (high concentration, low temp)
note: NO defect in anything
What is acyclovir and how does it work?
antiviral used to treat herpes and chicken pox
acts like a nucleoside in DNA formation and binds with phosphate –> blocks thymidine kinase and inhibits DNA formation
What is the sequence of molecules in purine synthesis?
RiPPIA
Ribose-5-P –> PRPP –> PRA –> IMP –> AMP and GMP
what does thymine kinase do? What is it inhibited by?
catalyzes deoxythyuridine to dTTP in pyrimidine salvage
inhibitted by acyclovir
What enzyme is essential in GMP and IMP (purine) salvage? What is its co-enzyme?
Hypoxanthine-guanine phosphoribosyl transferase
(HGPT)
Guanine or Hypoxanthine –HGPT–>GMP/IMP
PRPP is the co-enzyme
What does adenosine deaminase do and what is its clinical relevance?
adenosine –> inosine (in Purine salvage)
when in excess –> hemolytic anemia
when deficient –> SCID
what does the enzyme CPS II do?
gln –> carbamoyl phosphate in pyrimidine synthesis
What is 5-fluorouracil and what does it do?
Cancer drug more potent than methotrexate
blocks thymidylate synthase, which gets UMP to thymine derivatives in pyrimidine synthesis and stops production of DNA
How is gout treated? What increases when it is treated?
allopurinol inhibits xanthine oxidase (hypoxanthine –> xanthine –>uric acid)
hypoxanthine and xanthine increase, but are more water soluble that uric acid so don’t cause symptoms
What enzyme is essential in AMP (purine) salvage?
Adenine phophoribosyltransferase
(APRT)
A –APRT–>AMP
What does methotrexate do?
cancer drug that inhibits PRA –>IMP in purine synthesis
by acting as a competitive inhibitor with folate
How do sulfa drugs work?
Inhibit PABA –> folate in bacteria only
What is the basic path of thymine salvage?
thymine –> deoxythuridine –>–>dTTP
What does PRPP synthetase do?
Ribose-5-P to PRPP in purine synthesis
What is the sequence of Purine (AMP) degradation?
AMP –> adenosine –> Inosine –> hypoxanthine –> xanthine –> uric acid
What disease is associated with a decreased function in HGPRT? What are some symptoms?
Lesch-Nyhan syndrome. Inhibits purine salvage. Symptoms: increased uric acid, poor muscle control mental retardation, tendency to self-mutilate
What are the steps of pyrimidine synthesis?
GCCDOUT
glutamine –> carbamoyl phosphate –> carbamoyl aspartate –> dehydroorate –> orate –> UMP –> thymine and cytosine derivatives
What is orotic aciduria and how is it treated?
defect in UMP synthases, treated with oral uridine
