Drugs Affecting Nucleotide Metabolism

Question 1

What does Allopurinol do?

Answer 1

It inhibits XANTHINE OXIDASE. So now Hypoxanthine and xanthine cannot be converted to uric acid

Question 2

What happens to the Hypoxanthine and Xanthine that accumulates?

Answer 2

It is salvaged by HGPRT to IMP and XMP. The increased purine nucleotide pools will inhibit the rate-limiting enzymes in purine biosynthesis: PRPP syntheses and PRPP amidotransferases.

Also when these two are elevated, they can clear bases for excretion in urine

Question 3

What is Methotrexate?

Answer 3

Cancer drug that binds with high affinity to Dihydrofolate Reductase (DHFR) . This causes cells to accumulate the dihydrofolate form of folic acid and now cells are depleted of precursors needed for purine and pyrimidine biosynthesis

Question 4

What does Fluorouracil do?

Answer 4

It inhibits Thymidylate synthesis and DNA synthesis is inhibited

Question 5

What does Mercaptopurine do?

Answer 5

Inhibits PRPP amidotransferase and PRPP synthetase