Biochem- Nucleotide Metabolism III & IV

Question 1

What are the precursors for Pyrimidine synthesis?

Answer 1

Asparate
Glutamine
Carbonate

Question 2

What is the key of Pyrimidine synthesis?

Answer 2

Carbamoyl phosphate synthetase II (isoform)

Question 3

Describe the Synthesis of Pyrimidine.

Answer 3

1. CO2 + Glutamine + Asparate — CAP synthase II — CAP
2. CAP + Asparate acid — Asparate transcarbamoylase — Carbamoyl asparate acid (CAA)
3. CAA — dihydro-orotase — Dihydroorotic acid (DHOA)
4. DHOA — dihydoorotic dehydrogenase— orotic acid (OA)
5. OA — oratate phosphoribosyltransferase — orotidylate (OMP)
6. OMP — orotidylic acid de carboxylase — uridylate (UMP)
7. UMP — UDP

Question 4

Discuss how UDP is converted to (1) CTP and (2) dTMP.

Answer 4

1. UDP — UTP — Cytidylate (CTP) (CTP synthase)
2. UDP — dUDP (via ribonucleotide reductase) — dUMP — thymidylate (dTMP) (TMP synthase)

Question 5

State the regulation of Pyrimidine synthesis regulation.

Answer 5

1. CAP synthase II
   — Inhibited by UTP
   — activated by ATP and PRPP
2. Asparate transcarnbamoylase
   — inhibited by CTP
   — activates by ATP

Question 6

What is the effect of pyrimidine nucleotides feedback?

Answer 6

It inhibits PRPP synthase rxn

Question 7

State the disorders of Pyrimidine Metabolism

Answer 7

A. Hyperuricemia
B. Vitamin b12 (Cobalamin) and Folate
C. Orotic acidurias
D. Dihydropyrimidine Dehydrogenase Deficiency

Question 8

State the characteristics of Orotic Acidurias.

Answer 8

1. Orotate excreted in urine
2. Type 1 - orotate phosphoribosyltransferase and orotidylate decarboxylase
3. Type 2 — orotidylate decarboxylase
4. Seen in Reye’s syndrome
5. Allopurinol

Question 9

State the characteristics of Dihydropyrimidine Dehydrogenase Deficiency.

Answer 9

— degradation disorder
— caused by mutation in DPD gene
— susceptibility to fluoropyrimidines