Purine and Pyrimidine Metabolism Flashcards
What are nucleosides?
They are bases with the sugar group attached
What are nucleotides?
They are bases with the sugar group AND phosphate group(s)
What are the purines?
Adenine and guanine (2 rings)
What are the pyrimidines?
Cytosine, uracil and thymine (1 ring)
What is the order of purine biosynthesis?
The purine ring is built atom by atom onto the ribose group
What are the constituents that make up the purine ring?
- Aspartate
- Glycine
- Glutamine
- CO2
- N^10-Formyl-FH4
What is the first step of purine ring synthesis?
Ribose-5-Phosphate -> PRPP
R-5-Pi is activated
What is the second step of purine ring synthesis?
PRPP -> 5-phosphoribosylamine
Which is the regulated step of purine ring synthesis?
The second step:
PRPP -> 5-phosphoribosylamine
What is the enzyme catalyzing this reaction:
PRPP -> 5-phosphoribosylamine
Glutamine PRPP Amidotransferase
Where does ribose-5-phosphate in purine synthesis come from?
Pentose Phosphate Pathway
What nucleotide can branch into GMP or AMP?
IMP (inosinic acid)
How does allosteric inhibition of Glutamine PRPP Amidotransferase occur?
AMP and GMP are allosteric inhibitors of Glutamine PRPP Amidotransferase -> so it is negative feedback from the products
What is the function of 6-mercaptopurine?
It is an anti tumor agent that functions because it is converted into a nucleotide that will inhibit various steps of the purine synthesis, including Step 2, the rate limiting step
What are the constituents that make up the pyrimidine ring?
- Aspartate
- Glutamine
- CO2
What is the synthesis order of the pyrimidine ring?
Pyrimidine ring is synthesized FIRST separately from the ribose-5-phosphate and then it is attached to it
What is the regulated step of pyrimidine synthesis?
Glutamine + CO2 + ATP -> Carbamoyl Phosphate
What is the enzyme catalyzing the rate limiting step of pyrimidine synthesis?
Carbamoyl phosphate synthetase II
What is the pyrimidine precursor?
UMP
How does leflunomide treat arthritis?
Blocks pyrimidine synthesis by blocking dihydroorotate dehydrogenase
What enzyme converts dUMP to dTMP?
Thymidylate Synthase
What is the source of the methyl group for the conversion of dUMP to dTMP?
N^5/N^10-methylene THF
How does the anti tumor drug 5-fluorouracil work?
It is converted to f-dUMP which covalently binds to thymidylate synthase and inhibits the conversion of dUMP to dTMP.
What is the advantage of 5-fluorouracil in its side effects on normal cells?
As it only affects the conversion of dUMP, DNA synthesis is inhibited while RNA synthesis remains in tact.
How does the anti tumor agent methotrexate function?
It functions by inhibiting the function of dihydrofolate reductase which prevents the conversion of dihydrofolate to THF. This results in an accumulation of DHF which is toxic to the cell.
What is the function of ribonucleotide reductase?
It acts on the ribonucleotide-5’-diphosphate to form deoxyribonucleotide-5’-diphosphate
What is the cofactor necessary for the reaction catalyzed by ribonucleotide reductase?
Thioredoxin
Which hydroxyl group of ribose is converted to hydrogen?
2’ group
What is a drug that acts as an inhibitor of ribonucleotide reductase?
Hydroxyurea
What is the function of HGPRTase?
There are 2 reactions:
Hypoxanthine + PRPP -> IMP + PPi
Guanine + PRPP -> GMP + PPi
What is deficient in Lesch-Nyhan Syndrome?
HGPRTase
What is HGPRTase?
Hypoxanthine-Guanine Phosphoribosyltransferase
What is the final product of purine degradation in humans?
Uric Acid
What is the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid?
Xanthine Oxidase
What is uric acid found as in blood?
Urate
What are some consequences of overproduction or under secretion of uric acid?
Gout
How does allopurinol work to treat gout?
It inhibits xanthine oxidase so that less uric acid is fomed
