Metabolism XI: Purine & Pyrimidine Nucleotide Metabolism

Question 1

Where does THF come from?

Answer 1

folic acid (vitamin B9)

Question 2

Which type of blood condition can a folate deficiency cause?

Answer 2

megaloblastic anemia

• mature RBCs can grow but not divide due to inability to replicate and synthesize DNA (cell cannot progress from growth stage to mitosis)
• growth of RBCs without division weakens their membrane, causing them to break open

Question 3

How is vitamin B12 related to a folate deficiency?

Answer 3

It serves as a cofactor for the conversion of 5-methyl-THF to THF. Without vitamin B12, the body is stuck with THF in a useless form.

Question 4

What is the activated form of ribose-5-phosphate, and what is it used for?

Answer 4

PRPP is the activated form, and it represents the first step of purine biosynthesis.

Question 5

What is the committed/regulatory/rate-determining step of purine biosynthesis?

Answer 5

conversion of PRPP to 5-phosphoribosylamine via glutamine PRPP amidotransferase

Question 6

Which pathway does the anti-tumor agent, 6-mercaptopurine, inhibit?

Answer 6

purine biosynthesis (6-mercaptopurine is converted to a nucleotide, which then inhibits purine biosynthesis at steps 2, 12a, 12b, and 13a)

Question 7

Which disease is 6-mercaptopurine effective in treating?

Answer 7

acute lymphocytic leukemia (ALL)

Question 8

Which pathway is blocked by the rheumatoid arthritis drug, leflunomide?

Answer 8

pyrimidine biosynthesis

Question 9

Why is the synthesis of dTMP a good target for anti-tumor agents?

Answer 9

This is because thymine is only found in DNA, so blocking thymine synthesis means that we are only affecting DNA and not RNA synthesis (and therefore not affecting the body’s RNA and synthesis of proteins).

Question 10

Which pyrimidine nucleotide is synthesized first and serves as a precursor for the synthesis of other pyrimidine nucleotides?

Answer 10

UMP (can be converted to UTP, CTP, dCTP, dTTP)

Question 11

What is 5-fluorouracil used to treat?

Answer 11

carcinoma of breast, ovary, colon, prostate, pancreatic, head, and neck

Question 12

How does methotrexate serve as an antitumor agent?

Answer 12

It competitively binds to the active site of dihydrofolate reductase, making it such that dihydrofolate cannot bind and be converted to THF. Decreased intracellular THF=decreased purine and pyrimidine synthesis.

Question 13

What is methotrexate used to treat?

Answer 13

acute lymphoblastic leukemia (in children), certain carcinomas, rheumatoid arthritis, severe psoriasis

Question 14

What is the final product of purine degradation in humans?

Answer 14

uric acid

Question 15

What is the enzyme that catalyzes the conversion of hypoxanthine to xanthine, and xanthine to uric acid?

Answer 15

xanthine oxidase