13: Nucleotide Metabolism Flashcards
Purine vs pyrimidine rings
Purine: 2 rings
Pyrimidine: 1 ring
Nucleoside vs nucleotide parts
Nucleoside: N base + sugar
Nucleotide: N base + sugar + phosphate
Two places where nucleosides play roles
Adenosine, vitamin B12
De novo synthesis of pyrimidines vs purines
Pyrimidines: form ring structure then add PRPP
Purines: form PRPP and form the rings on top of that
Salvage pathway of purines
Adding R5P to the pre-formed purine base
Salvage pathway of pyrimidines
Forming pyrimidines from pyrimidine bases in RNA/DNA
Site for de novo synthesis vs salvage pathways
De novo: cytosol (+mito for pyrimidines)
Salvage: organelles
What organ does de novo synthesis take place in?
Liver
What is notable about all intermediates of purine de novo synthesis
All intermediates are phosphorylated due to phosphate group on R5P
Carbon sources for purine de novo synthesis
- 2C from folate
- 1C from CO2
- Rest of Cs: Gln, Gly, Asp
Major regulatory process in purine de novo synthesis and which four enzymes it affects
Feedback inhibition
- PRPP synthetase
- Phosphoribosyl pyrophosphate aminotransferase
- Adenylosuccinate synthase
- IMP dehydrogenase
What does elevated carbamoyl phosphate cause?
Hyperammonemia with orotic acid
What are the major branching points in pyrimidine and purine synthesis?
Purine: IMP
Pyrimidine: UMP
dUMP loop purpose
Is wasteful, but occurs so that dUTPase keeps dUTP low to prevent incorporation into DNA
Organs where PPP takes place
RBCs, liver, testes, mammary glands, adrenal cortex
Oxidation of purines during de novo synthesis
Oxygen is added to molecules as the pathway progresses, making them more and more polar
Four molecules in the purine de novo synthesis pathway that exhibit oxidation levels increasing
- Adenosine = 0 Oxygen
- Guanine / hypoxanthine = 1 oxygen
- Xanthine = 2 oxygen
- Uric acid = 3 oxygen
Primary vs secondary hyperuricemia
Primary: overproduction of uric acid
Secondary: underexcretion of uric acid
Why does gout occur in more distal joints?
Decreased temp in extremities = decreased uric acid solubility
What does overproduction of ADA (adenosine deaminase) cause?
Hemolytic anemia
Which is more dominant for purines, de novo synthesis or salvage pathway?
Salvage pathway
Purine salvage pathway: enzyme that generates AMP
APRT (adenosine phosphoribosyltransferase
Purine salvage pathway: generates GMP or IMP
HGPRT (hypoxanthine-guanine phosphoribosyltransferase)
What is Lesch-Nyhan Syndrome called when there is 8%+ of HGPRT still function + the symptoms
Kelley-Seegmiller syndrome - no neurologic symptoms, gout, kidney
