nucleotide

[noo-klee-uh-tahyd, nyoo-]

nucleotide, organic substance that serves as a monomer in forming nucleic acids. Nucleotides consist of either a purine or a pyrimidine base, a ribose or deoxyribose, and a phosphate group. Adenosine triphosphate serves as the principle energy carrier for the cell's reactions. The most important nucleotides are those derived from the bases adenine, guanine, cytosine, thymine, and uracil.

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nucleotide

Any of a class of organic compounds, including the structural units of nucleic acids. Each consists of a nucleoside and one or more phosphate groups. In nucleic acids, the phosphate of one nucleotide joins to the sugar of the next to form the backbone. Important nucleotides that are not part of nucleic acids include ATP, cyclic AMP (needed in glycogen breakdown), and certain coenzymes.

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Encyclopedia Britannica, 2008. Encyclopedia Britannica Online.

Nucleotide

Nucleotides are organic compounds that consist of three joined structures: a nitrogenous base, a sugar, and a phosphate group. The most common nucleotides can be divided into two groups (purines and pyrimidines) based on the structure of the nitrogenous base. The joined sugar is either ribose or deoxyribose.

Nucleotides are the structural units of RNA and DNA. They also serve as important cofactors in cellular signaling and metabolism. These cofactors include CoA, flavin adenine dinucleotide, flavin mononucleotide, adenosine triphosphate and nicotinamide adenine dinucleotide phosphate.

Nucleotide synthesis and structure

A nucleotide is composed of a ring of nitrogen, carbon and oxygen atoms, a five carbon sugar (together referred to as a nucleoside) and one phosphate group. Nucleotides can be synthesized through a variety of methods both in vitro and in vivo. This can involve salvage synthesis (the re-use of parts of nucleotides in resynthesizing new nucleotides through breakdown and synthesis reactions in order to exchange useful parts), or the use of protecting groups in a laboratory. In the latter case, a purified nucleoside or nucleobase is protected to create a phosphoramidite, and can be used to obtain analogues not present in nature and/or to create an oligonucleotide.

The first step of nucleotide synthesis is the formation of a nucleoside (the nitrogenous base joined to a sugar). The sugar involved in the synthesis and structure of a nucleotide may be either ribose or deoxyribose; in the latter case, the prefix 'deoxy' may be added before the name of the nucleoside in all cases except Uracil. A functional group of phosphate is then esterified to the sugar, creating a nucleotide. The phosphate group may consist of one, two, or three phosphates, forming monophosphates, diphosphates, or triphosphates, respectively.

Synthesis

Nucleotides can be synthesized through a variety of methods both in vitro and in vivo. This can involve salvage synthesis (the re-use of parts of nucleotides in resynthesizing new nucleotides through breakdown and synthesis reactions in order to exchange useful parts), or the use of protecting groups in a laboratory. In the latter case, a purified nucleoside or nucleobase is protected to create a phosphoramidite, and can be used to obtain analogues not present in nature and/or to create an oligonucleotide.

Types of bases

Nucleotides can be synthesized with both purine and pyrimidine as bases. In DNA, the purine bases are adenine and guanine, while the pyrimidines are thymine and cytosine. RNA uses uracil rather than thymine (thymine is produced by adding a methyl to uracil). The nucleotide passes through numerous biochemical steps while being processed, adding and removing atoms through the use of numerous enzymes.

Pyrimidine ribonucleotides

The synthesis of a single pyrimidine is complex; the diagram to the left demonstrates the synthesis of a single pyrimidine.

Purine ribonucleotides

The atoms which are used to build the purine nucleotides come from a variety of sources:

	The biosynthetic origins of purine ring atoms N1 arises from the amine group of Asp C2 and C8 originate from formate N3 and N9 are contributed by the amide group of Gln C4, C5 and N7 are derived from Gly C6 comes from HCO₃^- (CO₂)

The de novo synthesis of purine nucleotides by which these precursors are incorporated into the purine ring, proceeds by a 10 step pathway to the branch point intermediate IMP, the nucleotide of the base hypoxanthine. AMP and GMP are subsequently synthesized from this intermediate via separate, two step each, pathways. Thus purine moieties are initially formed as part of the ribonucleotides rather than as free bases.

Six enzymes take part in IMP synthesis. Three of them are multifunctional:

GART (reactions 2, 3, and 5)
PAICS (reactions 6, and 7)
ATIC (reactions 9, and 10)

Reaction 1. The pathway starts with the formation of PRPP. PRPS1 is the enzyme that activates R5P, which is primarily formed by the pentose phosphate pathway, to PRPP by reacting it with ATP. The reaction is unusual in that a pyrophosphoryl group is directly transferred from ATP to C1 of R5P and that the product has the α configuration about C1. This reaction is also shared with the pathways for the synthesis of the pyrimidine nucleotides, Trp, and His. As a result of being on (a) such (a) major metabolic crossroad and the use of energy, this reaction is highly regulated.

Reaction 2. In the first reaction unique to purine nucleotide biosynthesis, PPAT catalyzes the displacement of PRPP's pyrophosphate group (PP_i) by Gln's amide nitrogen. The reaction occurs with the inversion of configuration about ribose C1, thereby forming β-5-phosphorybosylamine (5-PRA) and establishing the anomeric form of the future nucleotide. This reaction which is driven to completion by the subsequent hydrolysis of the released PP_i, is the pathway's flux generating step and is therefore regulated too.