dTTP

dTTP, or deoxythymidine triphosphate, is one of the four deoxyribonucleotide triphosphates that supply the building blocks for DNA synthesis. It consists of a deoxyribose sugar, the thymine base, and three phosphate groups. During DNA replication, DNA polymerases incorporate a dTTP molecule opposite an adenine on the template strand, releasing pyrophosphate and providing the energy necessary for chain elongation.

Biosynthesis and pools of dTTP arise through de novo and salvage pathways. In de novo synthesis, thymidylate synthase converts dUMP to dTMP, which is then phosphorylated to dTDP by thymidylate kinase and finally to dTTP by a nucleoside diphosphate kinase. In the salvage pathway, thymidine kinase converts thymidine to dTMP, which can then be processed to dTDP and dTTP in the same way. Cellular dNTP pools are interconnected and tightly regulated to ensure balanced supply for accurate DNA replication and repair.

dTTP levels are influenced by cell cycle stage and metabolism; imbalances among the dNTP pools can increase replication errors and genomic instability. The dTTP pool can be decreased by inhibitors of thymidylate synthesis, such as 5-fluorouracil and methotrexate, which are used clinically as anticancer or antiparasitic agents. Conversely, excess dTTP can hinder replication fidelity. Cells maintain dTTP homeostasis through coordinated regulation of thymidylate synthase, thymidylate kinase, and nucleoside diphosphate kinase activities, as well as salvage pathways.

Measurement and study of dTTP levels are common in biochemistry and pharmacology to assess nucleotide metabolism, drug effects, and DNA synthesis capacity.