nucleotide

Any of various compounds consisting of a nucleoside combined with a phosphate group and forming the basic constituent of DNA and RNA.

[Alteration of NUCLEOSIDE.]

A cellular constituent that is one of the building blocks of ribonucleic acids (RNA) and deoxyribonucleic acid (DNA). In biological systems, nucleotides are linked by enzymes in order to make long, chainlike polynucleotides of defined sequence. The order or sequence of the nucleotide units along a polynucleotide chain plays an important role in the storage and transfer of genetic information. Many nucleotides also perform other important functions in biological systems. See also Coenzyme; Cyclic nucleotides; Nucleic acid.

Nucleotides are generally classified as either ribonucleotides or deoxyribonucleotides. Both classes consist of a phosphorylated pentose sugar that is linked via an N-glycosidic bond to a purine or pyrimidine base. The combination of the pentose sugar and the purine or pyrimidine base without the phosphate moiety is called a nucleoside. See also Purine; Pyrimidine.

Compounds of purine or pyrimidine base with a sugar phosphate. Natural constituents of human milk, often used to supplement infant formulae.

Nucleotides are the building blocks of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Individual nucleotide monomers (single units) are linked together to form polymers, or long chains. DNA chains store genetic information, while RNA chains perform a variety of roles integral to protein synthesis. Individual nucleotides also play important roles in cell metabolism.

Structure

The nucleotide molecule contains three functional groups: a base, a sugar, and a phosphate (see diagram). It may seem puzzling that a nucleic acid should contain a base. While the base portion does have weakly basic properties, the nucleotide as a whole acts as an acid, due to the phosphate group.

The names DNA and RNA are generated from the deoxyribose and ribose sugars found in these two polymers. Both are five-carbon sugars, whose carbons are numbered around the ring from 1′ to 5′ ("one prime" to "five prime"). The prime distinguishes the carbons on the sugar from the carbons on the base. The sugar in RNA nucleotides is ribose. The sugar in DNA is 2′-deoxyribose, which lacks an-OH group at the 2′ position. This small difference has some important consequences: The extra oxygen in RNA interferes with double helix formation between RNA chains (though it does not completely prevent it), and makes RNA more susceptible than DNA to base-catalyzed cleavage (breakdown into individual monomers).

A base attaches to the sugar at the sugar's 1′ position. Because of their nitrogen content, the bases are called nitrogenous bases, and are further classified as either purines or pyrimidines. Purine structures have two rings, while pyrimidines have one. The two purine bases found in both DNA and in RNA are guanine (G) and adenine (A). The two pyrimidine bases found in DNA are cytosine (C) and thymine (T), and the two pyrimidine bases found in RNA are cytosine and uracil (U). The only difference between thymine and uracil is the presence of a methyl group in thymine that is lacking in uracil. A base plus a sugar is called a nucleoside.

The phosphate groups are linked to the sugars at the 5′ position. The addition of one to three phosphate groups generates a nucleotide, also known as a nucleoside monophosphate, nucleoside diphosphate, or nucleoside triphosphate. For instance, guanosine triphosphate (GTP) is an RNA nucleotide with three phosphates attached. Deoxycytosine monophosphate (dCMP) is a DNA nucleotide with one phosphate attached.

Adenosine triphosphate, ATP, is the universal energy currency of cells. The breakdown of energy-rich nutrients is coupled to ATP synthesis, allowing temporary energy storage and transfer. When the ATP is later broken back down to ADP or AMP (adenosine diphosphate or monophosphate), it provides energy to power cell reactions such as protein synthesis or cell movement.

Polymer Formation

DNA and RNA polymers are constructed by forming phosphodiester bonds between nucleotides. In this arrangement, a phosphate group acts as a bridge between the 5′ position of one sugar and the 3′ position of the next. This arrangement is called the "sugar-phosphate backbone" of DNA or RNA; the bases hang off to the side.

In the cell, DNA or RNA polymers are synthesized using nucleoside triphosphate monomers as precursors. During polymer synthesis, two of the phosphate groups of the incoming nucleoside triphosphate are cleaved off, and this provides the energy needed to power the reaction. The remaining phosphate takes its place in the sugar-phosphate backbone of the growing nucleic acid chain. A pyrophosphate molecule (two linked phosphates) is released.

Just as an arrow has a tip and a tail, DNA or RNA chains have directionality, due to the structure of the sugar. At one end of a chain, a 5′ carbon will be left free. This is known as the 5′ end of the chain. At the other end, the 3′ carbon will be free; this is the 3′ end of the chain. Segments of DNA that are not free at their ends can also be discussed in terms of their 5′ and 3′ ends. This directionality has important consequences. When DNA replication occurs, it always moves from the 5′ end to the 3′ end, and the incoming triphosphate joins the 3′ end of the chain. Transcription (RNA synthesis from a DNA gene) also moves in this 5′-to-3′ direction. The 5′ end is considered the "upstream" end of the gene, and is the end on which the gene promoter (the transcription initiator) is located.

The Double Helix of Dna

In the double helix of DNA, guanine nucleotides are base-paired opposite cytosine nucleotides. Adenine nucleotides are base-paired opposite thymine nucleotides. This pairing is due to the complementary natures of the structures involved. Note that G is a two-ringed purine, while its partner C is a one-ringed pyrimidine. Similarly, A is a purine and T is a pyrimidine. These pairings give the interior of the helix a fixed diameter, without bulges or gaps. Just as importantly, the arrangement of atoms in the rings allows the partners to form sets of weak attractions, called hydrogen bonds, across the interior of the helix. The hydrogen bonds contribute greatly to the stability of the double helix, and the specificity of the G-C, A-T pairing is the structural basis of faithful replication of DNA.

Bibliography

Watson, James. The Double Helix: A Personal Account of the Discovery of the Structure of DNA. New York: Atheneum, 1968.

Stryer, Lubert. Biochemistry, 4th ed. New York: W. H. Freeman, 1995.

—Fred Perrino

For more information on nucleotide, visit Britannica.com.

The molecules that form the basic modular structure of the double helix of the DNA molecule. A nucleotide consists of three molecules — a sugar, a phosphate group, and a molecule called a base. If the double helix is a twisted ladder, the sugar and phosphates form the sides of the ladder and pairs of bases form the rungs. There are four different bases, usually abbreviated A, C, G, and T for adenine, cytosine, guanine, and thymine). The order of bases in DNA determines the genetic code.

Any of a group of compounds obtained by hydrolysis of nucleic acids, consisting of a purine or pyrimidine base linked to a sugar (ribose or deoxyribose), which in turn is esterified with phosphoric acid. See also nucleoside, deoxyribonucleic acid.

• cyclic n's — those in which the phosphate group bonds to two atoms of the sugar forming a ring, as in cyclic AMP and cyclic GMP, which act as intracellular second messengers.
• n. sequences — see dna sequencing.
• single n. polymorphisms (SNPs) — single base pair changes that distinguish one individual from another of the same species.

This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please improve this article by introducing more precise citations where appropriate. (February 2008)

Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. Additionally, nucleotides play central roles in metabolism. In that capacity, they serve as sources of chemical energy (adenosine triphosphate and guanosine triphosphate), participate in cellular signaling (cyclic guanosine monophosphate and cyclic adenosine monophosphate), and are incorporated into important cofactors of enzymatic reactions (coenzyme A, flavin adenine dinucleotide, flavin mononucleotide, and nicotinamide adenine dinucleotide phosphate).^[1]

Figure 1: Structural elements of the most common nucleotides

Contents 1 Nucleotide structure 2 Synthesis 2.1 Pyrimidine ribonucleotides 2.2 Purine ribonucleotides 3 Length unit 4 References 5 See also 6 External links

Nucleotide structure

Figure 2: Ribose structure indicating numbering of carbon atoms

A nucleotide is composed of a nucleobase (nitrogenous base) and a five-carbon sugar (either ribose or 2'-deoxyribose), and one to three phosphate groups. Together, the nucleobase and sugar comprise a nucleoside. The phosphate groups form bonds with either the 2, 3, or 5-carbon of the sugar, with the 5-carbon site most common. Cyclic nucleotides form when the phosphate group is bound to two of the sugar's hydroxyl groups.^[1] Ribonucleotides are nucleotides where the sugar is ribose, and deoxyribonucleotides contain the sugar deoxyribose. Nucleotides can contain either a purine or pyrimidine base.

Nucleic acids are polymeric macromolecules made from nucleotide monomers. In DNA, the purine bases are adenine and guanine, while the pyrimidines are thymine and cytosine. RNA uses uracil in place of thymine.

Synthesis

Nucleotides can be synthesized by a variety of means both in vitro and in vivo. In vivo, nucleotides can be synthesised de novo or recycled through salvage pathways.^[2] Nucleotides undergo breakdown such that useful parts can be reused in synthesis reactions to create new nucleotides. In vitro, protecting groups may be used during laboratory production of nucleotides. A purified nucleoside is protected to create a phosphoramidite, which can then be used to obtain analogues not found in nature and/or to synthesize an oligonucleotide.

Pyrimidine ribonucleotides

The synthesis of UMP.

The color scheme is as follows: enzymes, coenzymes, substrate names, inorganic molecules

Pyrimidine nucleotide synthesis starts with the formation of carbamoyl phosphate from glutamine and CO₂. The cyclisation reaction between carbamoyl phosphate reacts with aspartate yielding orotate in subsequent steps. Orotate reacts with 5-phosphoribosyl α-diphosphate (PRPP) yielding orotidine monophosphate (OMP) which is decarboxylated to form uridine monophosphate (UMP). It is from UMP that other pyrimidine nucleotides are derived. UMP is phosphorylated to uridine triphosphate (UTP) via two sequential reactions with ATP. Cytidine monophosphate (CMP) is derived from conversion of UTP to cytidine triphosphate (CTP) with subsequent loss of two phosphates.^{[3] [4]}

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 synthesis of IMP. The color scheme is as follows: enzymes, coenzymes, substrate names, metal ions, inorganic molecules

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.

Length unit

Nucleotide (abbreviated nt) is a common length unit for single-stranded RNA, similar to how base pair is a length unit for DNA. A RNA molecule made up by 1,000 nucleotides is 1,000 nt long, or 1 kilonucleotide (knt).

References

1. ^ ^{a b} Alberts B, Johnson A, Lewis J, Raff M, Roberts K & Wlater P (2002). Molecular Biology of the Cell (4th ed.). Garland Science. ISBN 0-8153-3218-1. pp. 120-121.
2. ^ Zaharevitz, DW; Anerson, LW; Manlinowski, NM; Hyman, R; Strong, JM; Cysyk, RL.. Contribution of de-novo and salvage synthesis to the uracil nucleotide pool in mouse tissues and tumors in vivo. 
3. ^ Jones, ME (1980). "Pyrimidine nucleotide biosynthesis in animals: Genes, enzymes, and regulation of UMP biosynthesis". Ann. Rev. Biochem 49: 253–79. doi:10.1146/annurev.bi.49.070180.001345. 
4. ^ McMurry, JE; Begley, TP (2005). The organic chemistry of biological pathways. Roberts & Company. ISBN 9780974707716. 

See also

• Chromosome
• Gene
• Genetics
• Biology
• Nucleic acid analogues

External links

• Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents (IUPAC)
• Provisional Recommendations 2004 (IUPAC)
• Chemistry explanation of nucleotide structure

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v • d • e Nucleobases, nucleosides, and nucleotides Nucleobases Purine (Adenine, Guanine, Purine analogue) · Pyrimidine (Uracil, Thymine, Cytosine, Pyrimidine analogue) Nucleosides/ (NB+pentose) Ribonucleosides Adenosine · Guanosine · Uridine · Cytidine Deoxyribonucleosides Deoxyadenosine · Deoxyguanosine · Thymidine · Deoxyuridine · Deoxycytidine Nucleotides/ (NS+phosphate) Ribonucleotide monophosphates (AMP, GMP, UMP, CMP) · diphosphates (ADP, GDP, UDP, CDP) · triphosphates (ATP, GTP, UTP, CTP) Deoxyribonucleotides monophosphates (dAMP, dGMP, dUMP, TMP, dCMP) · diphosphates (dADP, dGDP, TDP, dCDP) · triphosphates (dATP, dGTP, TTP, dCTP) Cyclic cAMP, cGMP, c-di-GMP, cADPR Major families of biochemicals Saccharides/Carbohydrates/Glycosides · Amino acids/Peptides/Proteins/Glycoproteins · Lipids/Terpenes/Steroids/Carotenoids · Alkaloids/Nucleobases/Nucleic acids · Cofactors/Flavonoids/Polyketides/Tetrapyrroles

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