Chapter 18 ( Purine And Pyrimidine Metabolism )

Question 1

Sources for purines and pyrimidines bases for salvage enzymes ?

Answer 1

1- synthesis in the liver and transport to other tissues

2- digestion of endogenous nucleic acids from cell death and RNA turnover

Question 2

2 causes for orotic aciduria ? Differences between them ?

Answer 2

1- Ornithin transcarbamoylase deficiency in urea cycle
Hyperammonemia
No megaloblastic anemia

2- UMP synthase deficiency in pyrimidine synthesis
No hyperammonemia
Megaloblastic anemia

Question 3

Carbamoyl phosphate synthase 2 ?

Answer 3

Cytoplasmic enzyme In pyrimidine synthesis uses : CO2 , glutamine , ATP to form Carbamoyl phosphate

Question 4

Hydroxyurea mechanism ?

Answer 4

Inhibition of Ribonucleotide reductase enzyme

Question 5

5-Fluorouracil mechanism ?

Answer 5

Inhibition of Thymidylate synthase

Question 6

Drugs that inhibit Dihydrofolate reductase ?

Answer 6

Methotrexate in eukaryotes
Trimethoprim in prokaryotes
Pyrimethamine in protozoa ( especially toxoplasma )

Question 7

Cotrimoxazole mechanism ?

Answer 7

Contains the synergistic antibiotics Sulfamethoxazole and Trimethoprim which inhibit different steps in the prokaryotic synthesis of tetrahydrofolate

Question 8

Ribonucleotide reductase function ? Inhibitors ?

Answer 8

Formation of deoxyribonucleotides for DNA synthesis , all 4 nucleotide substrates must be diphosphates
Its inhibitors : dADP , dATP

Question 9

Rate limiting enzyme of Purine synthesis ? Its natural and synthetic inhibitors ?

Answer 9

PRPP amidotransferase 
Natural inhibitors : 
AMP
IMP
GMP
Synthetic inhibitors :
Allopurinol nucleotide 
6-Mercaptopurine nucleotide

Question 10

Which amino acids are used in purine synthesis ?

Answer 10

Glycine
Aspartate
Glutamine