Nucleotide Metabolism

Question 1

Cause of Gout?

Answer 1

Accumulation of purine catabolic product. Uric acid. Mostly big toe joint. ADA deficiency. Chronic treated by allopurinol

Question 2

Purine numbering system

Answer 2

Counterclockwise, N-9 attached to sugar

Question 3

Pyrimidine C numbering system

Answer 3

Clockwise, sugar bound to N1

Question 4

Ribose5p and deoxyribose5p are produced by what?

Answer 4

Pentose phosphate pathway

Question 5

Are nucleotides ingested in diet used in metabolism?

Answer 5

No, usually excreted

Question 6

How are purines and pyrimidines made?

Answer 6

De Novo and Salvage.

Purines synthesized directly on PRPP, pyrimidines pre made and attached. De Novo needs ATP, in liver.

Question 7

What is the rate limiting step of nucleotide anabolism, and what enzyme is needed?

Answer 7

R5P and ATP to AMP and PRPP. Enzyme is PRPP synthetase

Question 8

How is PRPP committed to purine biosynthesis?

Answer 8

By PRPP amidotransferase. Adds amine and loses 2p.

Question 9

When is glutamine used in purine biosynthesis?

Answer 9

Twice, step 2 and 5.

Question 10

Result of initial steps or purine synthesis?

Answer 10

Inosine monophosphate, with hypoxanthine as base. Branch point for synthesis of AMP and GMP

Question 11

Steps for formation of adenylate from IMP?

Answer 11

Catalyze by adenylsuccinate synthetase. Aspartate added to c6 carbon. Needs GTP

Question 12

Steps for formation of guanylate from IMP?

Answer 12

Amine from glutamine added at c2 carbon. Catalyzed by GMP synthase. Activated by AMP attachment.

Question 13

Regulation of purine formation?

Answer 13

ATP needed to make GMP, and GTP needed to make AMP. Prevents an imbalance from forming

Question 14

AMP+ATP=2ADP

What enzyme does this?

Answer 14

Adenylate kinase

Question 15

GMP+ATP=GDP+ADP

What enzyme does this?

Answer 15

Guanylate kinase

Question 16

XDP+ATP=XTP+ADP

What enzyme does this?

Answer 16

Nucleotide diphosphate kinase

Question 17

Feedback regulation for purine synthesis?

Answer 17

First two steps inhibited by products. Step one inhibited by DP, two by MP.

Question 18

Pyrimidine biosynthesis steps?

Answer 18

Two things attached to make orotate, attached to PPRP to make OMP. Processed to make UMP. Glutamine makes CTP from UTP.

Question 19

How is TTP made?

Answer 19

From deoxyUMP only. Which is made by ribonucleotide reductase. Then thymidine synthase

Question 20

What is ribonucleotide reductase inhibited by?

Answer 20

Its products, such as dATP.

Question 21

Salvage reactions for nucleotide metabolism?

Answer 21

Attach free bases to PRPP. Most important enzyme is HGRPT, which attaches base to sugar.

Question 22

Nucleotide degradation?

Answer 22

Purines degraded to uric acid. Usually close to solubility limit, so increase is very bad

Question 23

ADA deficiency

Answer 23

ADA converts adenylate to inosylate. Alternative pathways not found for dAdenylate, so rapid cell division affected. Immunodeficiency

Question 24

Hyperuricemia causes

Answer 24

Increase in purine biosynthesis or degradation. Decreased excretion. Increased PRPP synthesis, or decreased HGRPT

Question 25

Lesch Nyhan syndrome

Answer 25

HGRPT problem leading to mental issues and self mutilation

Question 26

Hyperuricemia treatment?

Answer 26

NSAID, colchicine, increase renal excretion