Question

Describe the roles of dUTPase, thymidylate synthase, and dihydrofolate reductase in the synthesis of dTMP.

Short answer

The dUTPase produces dUMP from dUTP through the following reaction:

$dUTP+H_{2}O\underset{dATPase}{\to }dUMP+P{P}_i$

Thymidylate synthase produces dTMP from dUMP through the following reaction:

$dUMP+N^5,N^{10}-Methylenetetrahydrofolate\underset{thymidylatesynthase}{\to }dTMP+Dihydrofolate$

Dihydrofolate helps to restore by converting DHP to THF through the following reaction:

$DHF+NADH+H^{+}\underset{Dihydrofolatereductase}{\to }THF+NAD{P}^{+}$

Step-by-step solution

Role of dUTPase

The dUTPase, known as dUTP diphophohydrolase, hydrolyzes the deoxyuridine triphosphate (dUTP) to deoxyuridine monophosphate (dUMP). The reaction is as follows:

$dUTP+H_{2}O\underset{dATPase}{\to }dUMP+P{P}_i$

Role of thymidylate synthase

Thymidylate synthase is an enzyme that transfers a methyl group to the deoxyuridine monophosphate (dUMP), converting it into deoxythymidine monophosphate (dTMP). It involves the removal of methyl from $N^5,N^{10}-Methylenetetrahydrofolate$to produce dihydrofolate (DHF). The reaction is as follows:

$dUMP+N^5,N^{10}-Methylenetetrahydrofolate\underset{thymidylatesynthase}{\to }dTMP+Dihydrofolate$

Role of dihydrofolatereductase

The dihydrofolatereductase catalyzes the formation of tetrahydrofolate (THF) from the dihydrofolate (DHF) by reducing NADPH +$H^{+}$ to$NAD{P}^{+}$ . The reaction is as follows:

$DHF+NADH+H^{+}\underset{Dihydrofolatereductase}{\to }THF+NAD{P}^{+}$

The THF is converted to $N^5,N^{10}-Methylenetetrahydrofolate$by serine hydroxymethyl-transferase so that it can be used in dMP synthesis.