Nucleoside triphosphate

[2] Nucleoside triphosphates also serve as a source of energy for cellular reactions[3] and are involved in signalling pathways.

[8] The term nucleoside refers to a nitrogenous base linked to a 5-carbon sugar (either ribose or deoxyribose).

DNA contains four different nitrogenous bases: adenine, guanine, cytosine and thymine.

[16] These enzymes covalently link the free -OH group on the 3’ carbon of a growing chain of nucleotides to the α-phosphate on the 5’ carbon of the next (d)NTP, releasing the β- and γ-phosphate groups as pyrophosphate (PPi).

Given their importance in the cell, the synthesis and degradation of nucleoside triphosphates is under tight control.

[6] This section focuses on nucleoside triphosphate metabolism in humans, but the process is fairly conserved among species.

Both purine and pyrimidine synthesis use phosphoribosyl pyrophosphate (PRPP) as a starting molecule.

[23] Purine synthesis is regulated by the allosteric inhibition of IMP formation by the adenine or guanine nucleotides.

[27] TTP is not a substrate for nucleic acid synthesis, so it is not synthesized in the cell.

Instead, dTTP is made indirectly from either dUDP or dCDP after conversion to their respective deoxyribose forms.

[28] Ribonucleotide reductase (RNR) is the enzyme responsible for converting NTPs to dNTPs.

Given that dNTPs are used in DNA replication, the activity of RNR is tightly regulated.

When ATP or dATP is bound to the S site, RNR will catalyze synthesis of dCDP and dUDP from CDP and UDP.

[31] dADP is then phosphorylated to give dATP, which can bind to the A site and turn RNR off.

ATP synthase couples the synthesis of ATP from ADP and phosphate with an electrochemical gradient generated by the pumping of protons through either the inner mitochondrial membrane (cellular respiration) or the thylakoid membrane (photosynthesis).

When a ligand binds a GPCR, an allosteric change in the G protein is triggered, causing GDP to leave and be replaced by GTP.

[41] Once these nucleoside analogues enter a cell, they can become phosphorylated by a viral enzyme.

[8] Some less selective nucleoside analogues can be used as chemotherapy agents to treat cancer,[43] such as cytosine arabinose (ara-C) in the treatment of certain forms of leukemia.

Schematic showing the structure of nucleoside triphosphates. Nucleosides consist of a 5-carbon sugar (pentose) connected to a nitrogenous base through a 1' glycosidic bond. Nucleotides are nucleosides with a variable number of phosphate groups connected to the 5' carbon. Nucleoside triphosphates are a specific type of nucleotide. This figure also shows the five common nitrogenous bases found in DNA and RNA on the right.
In nucleic acid synthesis, the 3’ OH of a growing chain of nucleotides attacks the α-phosphate on the next NTP to be incorporated (blue), resulting in a phosphodiester linkage and the release of pyrophosphate (PP i ). This figure shows DNA synthesis, but RNA synthesis occurs through the same mechanism.
The energy released during hydrolysis of adenosine tripshophate (ATP), shown here, is frequently coupled with energetically unfavourable cellular reactions.
Binding of a ligand to a G protein-coupled receptor allows GTP to bind the G protein. This causes the alpha subunit to leave and act as a downstream effector.