Nucleoside triphosphate

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A nucleoside triphosphate (NTP) is a molecule containing a nucleoside bound to three phosphates (also known as a nucleotide). Nucleotide derivatives are necessary for life, as they are the building blocks of nucleic acids and have thousands of other roles in cell metabolism and regulation. NTPs generally provide energy and phosphate group for phosphorylations.

Natural nucleoside triphosphates include adenosine triphosphate (ATP), guanosine triphosphate (GTP), cytidine triphosphate (CTP), 5-methyluridine triphosphate (m5UTP), and uridine triphosphate (UTP). ATP is a major source of cellular energy. GTP is a very frequent cofactor of enzymes and proteins.

The terms ATP, GTP, CTP, and UTP refer to those nucleoside triphosphates that contain ribose. The nucleotide triphosphates containing deoxyribose are called dNTPs, and take the prefix deoxy- in their names and small d- in their abbreviations: deoxyadenosine triphosphate (dATP), deoxyguanosine triphosphate (dGTP), deoxycytidine triphosphate (dCTP), deoxythymidine triphosphate (dTTP) and deoxyuridine triphosphate. The dNTPs are the building blocks for DNA (they lose two of the phosphate groups in the process of incorporation).

Apart from (d)ATP, (d)GTP, (d)CTP, (d)TTP and (d)UTP, there are other less abundant NTPs, such as intermediates of nucleotide metabolism, but also "rare" natural nucleotides or even artificial nucleotides.[1] An example of rare NTPs are the tautomeric forms of some NTPs. They can cause mismatched base pairing during DNA replication. For example, a tautomeric form of cytosine is capable of forming 3 hydrogen bonds with adenine, and it will spontaneously tautomerize to its original cytosine form, causing a mismatch. By a similar token, the deamination of cytosine leads to uracil, whereas a deamination of a commonly encountered (in eukaryotes) 5-methylcytosine will lead to thymine. However, the 3' to 5' exonuclease activity of DNA polymerase III ensures that mismatched bases are excised during replication.

Generally nucleotides are nucleosides (a ribose/deoxyribose sugar covalently bonded to a nitrogenous base, such as adenine) that have 5' phosphate(s). However, for the sake of technical terminology, nucleotides are given classifications as nucleosides with a suffix describing the number of phosphates present in a specific unit. For example, if a nucleotide has one phosphate, it is a nucleoside monophosphate (NMP). If the nucleotide has two phosphates, then it is called a nucleoside diphosphate (NDP), and for three, it is a nucleoside triphosphate (NTP). The nucleotides that contain a ribose sugar are the monomers of RNA and those that contain a deoxyribose sugar compose DNA.

NTPs, NDPs and NMPs are ubiquitous in the cell cytoplasm, nucleus and organelles. Given their multifarious functions, their levels are under fairly tight metabolic control. Shifts in the ratio of available nucleotides can cause shifts in their incorporation, which, if not corrected, can lead to mutations. Most of the discussion on mutual ratios of nucleotides should belong under entry nucleotide, but concentrating strictly on the abundance of the triphosphorylated versions, we find that ATP spending is replenished by oxidative phosphorylation, while phosphorylation status of other nucleotides is regulated by NDP kinases (EC 2.7.4.6) and NMP kinases (EC 2.7.4.4) that use ATP pool as their cross-phosphorylation source.

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