Pyrimidine Biosynthesis

Question 0

4 nt binding sites in RNR

Answer 0

Activity site ATP n dATP, substrate specificity siteATP dTTP dGTP dATP, hexamerization site can bind ATP only (allosteric)

Substrate binding site ADP GDP UDP CDP

dTTP comes from dUMP!= DNAP can’t distinguish these 2 therefore prevent mutation by decreasing concentration of dUTP

Question 1

RNR =?

Answer 1

Ribonucleotide reductase

Question 2

Substrate specificity site bind which 4 nts

Answer 2

ATP dTTP dGTP dATP

Question 3

Substrate specificity site - ATP induces reduction of

Answer 3

CDP + UDP

Question 4

Substrate specificity site - dTTP induces reduction of

Answer 4

GDP

Question 5

Substrate specificity site - dGTP induces reduction of

Answer 5

ADP

Question 6

Substrate specificity site - dATP:

Answer 6

Inhibits reduction of all NDPs

dATP binds allosterically to the activity site to inhibit RNR

Question 7

What enzyme performs this rxn?

ATP + dNDP -> dNTP + ADP

Answer 7

Nucleoside diphosphate kinase

Question 8

dUTP TO dTTP?

Answer 8

1. Hydrolysis dUTP H2O to dUMP PPi
2. thymidylate synthase dUMP to dTMP
3. Thymidylate kinase dTMP to dTTP