Question

You want to look at the connection between ribonucleotide reductase and thymidylate synthase. You carry out an in vitro experiment (in a test tube) with wild-type ribonucleotide reductase and thymidylate synthase along with any additional enzymes needed. You also include in the test tube ribonucleotides (ATP, CDP, UDP, GDP, and ADP), 7,8-dihydrofolate, NADPH, serine, and an inhibitor of thymidylate synthase. List the diphosphate deoxyribonucleotides that will be produced as a result of this in vitro experiment. Discuss the effects of inhibiting the thymidylate synthase on the activity of the ribonucleotide reductase.

Answer 1

Under the vitro experiment; Deoxy ribo adenosine diphosphate, deoxy riboflavin gwanosine di phosphate, deoxyribo cytosine diphosphate as well as deoxyribouridine diphosphate are all formed.

The inhibitor of thymidylate synthase block the activity of this enzyme which would otherwise convert deoxyribo UDP to deoxyribo thymidine diphosphate.

Blocking this enzyme lowers down the thymidine diphosphate nucleotide concentration which interrupt the DNA replication. The ribonucleotide reductase is responsible for the reduction of respective nucleotides into their deoxyribonucleic forms which can be considered as precursors for DNA synthesis.

Deoxy Uridine diphosphare is also a product of this enzyme which is further modified by thymidylate synthase twhich converts into deoxy thymedine diphosphate. But this convertion is blocked in vitro experiment which leads to one nucleotide scarce for DNA replication.