Chapter 26, Problem 15P

Interpretation Introduction

Interpretation:

About the chemistry of dTMP synthesis and the substrate-binding site of thymidylate synthase.

Concept introduction:

Thymidylate synthetase is an accelerator that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to nucleotide (dTMP). Nucleoside is one amongst the nucleotides in deoxyribonucleic acid. With inhibition of TS, associate degree imbalance of deoxynucleotides and enlarged levels of dUMP arise. Each cause deoxyribonucleic acid injury.

Answer to Problem 15P

The balanced reaction is:

$\begin{array}{l}UMP+2ATP+NADPH+H^{+}+H_{2}O+N^5-N^{10}-methylene-THF\to \\ 2ADP+NAD{P}^{+}+2P_i+dTMP+DHF\end{array}$

Explanation of Solution

The following are the reactions concerned within the conversion of UMP and $N^5-N^{10}$ -methylene-THF to dTMP. Within the commencement, UMP is regenerated to UDP through the utilization of monophosphate enzyme. This is often followed by conversion of UDP to dUDP exploitation ribonucleotide enzyme. Then, dUDP is phosphorylated to grant dUTP, that is, regenerated to dUMP, and eventually dTMP.

  $UMP+ATP\to UDP+ADP$

$UDP+NADPH+H^{+}\to dUDP+NAD{P}^{+}+H_{2}O$

$dUDP+ATP\to dUTP+ADP$

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

$P{P}_i+H_{2}O\to 2P_i$

$dUMP+N^5-N^{10}-methylene-THF\to dTMP\to DHF$

Taking away like products and reactants.

$\begin{array}{l}UMP+ATP\to UDP+ADP\\ UDP+NADPH+H^{+}\to dUDP+NAD{P}^{+}+H_{2}O\\ dUDP+ATP\to dUTP+ADP\\ dUTP+H_{2}O\to dUMP+P{P}_i\\ P{P}_i+H_{2}O\to 2P_i\\ dUMP+N^5-N^{10}-methylene-THF\to dTMP+DHF\\ \end{array}$

This leaves us with a net reaction.

$\begin{array}{l}UMP+2ATP+NADPH+H^{+}+H_{2}O+N^5-N^{10}-methylene-THF\to \\ 2ADP+NAD{P}^{+}+2P_i+dTMP+DHF\end{array}$

The charged aspect chains of essential amino acid are wont to pull in negatively charged groups as seen within the catalyst thymidylate synthase. Note that Arg²³ and Arg²¹⁸ are on separate subunits than Arg¹⁷⁸and Arg¹⁷⁹.

Conclusion

The balanced reaction is:

$\begin{array}{l}UMP+2ATP+NADPH+H^{+}+H_{2}O+N^5-N^{10}-methylene-THF\to \\ 2ADP+NAD{P}^{+}+2P_i+dTMP+DHF\end{array}$