Purine and Pyrimidine Metabolism

Question 1

Purine synthesis

Answer 1

Synthesized de novo (new), ribose 5-phosphate is activated by PRPP synthetase adding phosphate groups, the base is then made while attached to the sugar

Question 2

Inosine monophosphate (IMP)

Answer 2

Ribose 5-phosphate is converted to IMP by 11 enzyme catalyzed reactions using 6 ATP, converted to adenine and guanine ribonucleotides

Question 3

Molecules contributing to purines

Answer 3

Almost entire glycine molecule- 2 C, 1 N
Formate- 2 C
Amide N of glutamine- 2 N
Aspartate- 1 N
CO2- 1 C

Question 4

IMP to AMP

Answer 4

IMP is converted to adenosine monophosphate (AMP) by two enzyme catalyzed reactions requiring 1 GTP, aspartate is the nitrogen donor to the purine ring, produces ATP

Question 5

IMP to GMP

Answer 5

IMP is converted to guanosine monophosphate (GMP) by two enzyme catalyzed reactions requiring 1 ATP, glutamine is the nitrogen donor to the purine ring, produces GTP

Question 6

Control of purine biosynthesis

Answer 6

Production of GMP and AMP regulated at three major points- two within the IMP synthesis pathway, one after IMP synthesis, end products inhibit IMP synthesis and their own synthesis

Question 7

Regulation with ATP and GTP

Answer 7

Production of AMP produces ATP which increases the rate of GMP production, production of GMP produces GTP which increases the rate of AMP production

Question 8

Points of regulation in IMP synthesis pathway

Answer 8

PRPP synthetase, glutamine phosphoribosyl amidotransferase

Question 9

Point of regulation after IMP synthesis

Answer 9

IMP dehydrogenase (GMP pathway), adenylosuccinate synthetase (AMP pathway)

Question 10

Purine salvage

Answer 10

Adenosine deaminase produces inosine, inosine and guanosine are converted to ribose 1-phosphate and free base by purine nucleoside phosphorylase

Question 11

Lesch-Nyhan syndrome

Answer 11

Defective hypoxanthine-guanine phosphoribosyltransferase, purines are not salvaged, are converted to uric acid

Question 12

Adenosine deaminase deficiency

Answer 12

Causes severe immune problems (lymphocytes use salvage pathway), body is unable to produce T or B cells, causes susceptibility to infection

Question 13

Pyrimidine synthesis

Answer 13

Base is made first, then added to ribose 5-phosphate, carbamoyl phosphate synthetase II uses glutamine and CO2 (regulation step), aspartate transcarbamoylase adds aspartate to carbamoyl phosphate

Question 14

Uridine monophosphate (UMP)

Answer 14

UMP is synthesized from glutamine in a reaction catalyzed by 6 enzymes requiring 2 ATP molecules, UMP is converted to UTP and CTP

Question 15

Molecules contributing to pyrimidines

Answer 15

Glutamine- 1 N
Bicarbonate- 1 C
Aspartate- 3 C, 1 N

Question 16

Pyrimidine salvage

Answer 16

Pyrimidine nucleoside phosphorylase converts free bases to nucleosides, nucleoside kinases produce the nucleotides

Question 17

Formation of deoxyribonucleotides

Answer 17

Ribose (NDP) have to be converted to deoxyribose (dNDP) by ribonucleotide reductase, removal of hydroxyl group and replacement with hydrogen

Question 18

Nucleoside diphosphate

Answer 18

Can be converted to triphosphate and used for DNA synthesis

Question 19

Regulation of deoxyribonucleotides

Answer 19

Reactions are tightly regulated, proper ratio is necessary for growth and function, deficiency in dNTP can be lethal

Question 20

Purine degradation

Answer 20

More likely to be salvaged than degraded (expensive to synthesize), those not salvaged are broken down to uric acid and excreted in urine