Nucleotides: Structure and Properties

Abstract

Nucleotides consist of a nitrogen‐containing base, a five‐carbon sugar and one or more phosphate groups. Cells contain many types of nucleotides, which are in constant flux between free and polymeric states. Nucleotides play central roles in many cellular processes, including metabolic regulation and the storage and utilisation of genetic information. The levels of nucleotides in cells are regulated efficiently due to the small pools of free nucleotides, with an exception being adenosine‐5′‐triphosphate, which is at higher concentrations due to its role as the universal currency of energy. Within cells, ribonucleotides are synthesised from simple building blocks or they are obtained via the recycling of preformed bases. Different types of cells have striking variations in their nucleotide composition as these are linked to the rate of cell growth; in mammals, the amounts of nucleotides and nucleic acids as a proportion of cell weight vary from approximately 1% in muscle to 15–40% in thymus gland and sperm cells.

Key Concepts

  • Nucleotides are relatively complex molecules that consist of three fundamental components: a nitrogenous base, a sugar and one (or more) phosphate groups.
  • A wide range of nucleotides are required for specific cellular functions, such as information transfer or signalling processes within and between cells; minor forms of nucleotides are particularly prevalent within stable RNAs (rRNA and tRNA) or as unwanted by‐products of reactions occurring within the cell.
  • Nucleotides exist as monomers and in polymeric forms, called nucleic acids, and there are two closely related types: ribonucleotides are present in ribonucleic acid (RNA) and deoxyribonucleotides, which are synthesised by the reduction of ribonucleotides, are present in deoxyribonucleic acid (DNA).
  • Nucleotides are in constant flux between their free and polymeric states, and their levels are regulated efficiently because cells have small pools of free nucleotides; an exception to this is adenosine‐5′‐triphosphate (ATP), which is more abundant due to its role as the universal currency of energy in biological systems, which arises from its high potential for phosphate transfer to other molecules.
  • The covalent structure of nucleotides are relatively stable, but they are involved in a variety of chemical reactions within the cell and can be broken down by acid‐catalysed hydrolysis, with purine nucleotides generally being more easily hydrolysed than pyrimidine nucleotides.
  • Within cells, ribonucleotides are synthesised de novo from simple building blocks or they are obtained via salvage pathways from the recycling of preformed bases, which is simpler and requires less energy than the de novo reactions.
  • Different types of cells have striking variations in their nucleotide composition because their amounts are linked to the rate of cell growth; nucleotides and nucleic acids are estimated to comprise 5–10% of the total weight of rapidly dividing bacteria, and in mammals, the amounts vary from approximately 1% in muscle to 15–40% in thymus gland and sperm cells.
  • The manner in which nucleotides interact with other molecules is determined predominantly by the manner by which charge is distributed across them, although a variety of atoms are available to interact with other molecules, particularly via hydrogen bond formation.
  • The major pyrimidine bases found in nucleotides are cytosine, thymine, uracil and orotate and, within cells, the majority of pyrimidine nucleotides exist in their polymeric form in DNA and RNA molecules; cytosine is found in both DNA and RNA, but uracil is only present within RNA and thymine is, in general, only found in DNA.
  • Purine nucleotides common to cellular metabolism contain the bases adenine, guanine, hypoxanthine and xanthine, and purine nucleotides that are synthesised for specific aspects of cellular metabolism include 3′,5′‐cyclic AMP, a range of nicotinamide–adenine dinucleotides (NAD+, NADH, NADP+, NADPH), flavin–adenine dinucleotide and coenzyme A (CoA).

Keywords: base; sugar; nucleoside; nucleotide; phosphate; pyrimidine; purine

Figure 1. Chemical structure of adenosine‐5′‐triphosphate (ATP), a nucleotide. All nucleotides consist of a base, a sugar and a phosphate ester. These constituent parts are shown for ATP, where the base is adenine (shown in green), the sugar is β‐d‐ribose (shown in purple), and the phosphate is a triphosphate attached to the 5′‐carbon of the sugar (shown in orange). The base‐and‐sugar moiety is referred to as a nucleoside (termed adenosine for the nucleoside shown). The base is joined to the sugar through the N‐glycosidic bond. The positions of atoms in the base and sugar are numbered. Purine bases contain atoms numbered 1–9 as shown, and pyrimidine bases are numbered 1–6 (see Figure). Atoms within the sugar (identified by the prime mark) are numbered similarly for all nucleotides containing β‐d‐ribose. Bond lengths are not drawn to scale.
Figure 2. Structures and tautomeric equilibria of the DNA bases. Atoms within bases are numbered, with N1 of pyrimidines and N9 of purines being bonded to C1′ of the sugar in nucleosides and nucleotides. Tautomeric forms shown to the left are the major ones and the imino and enol forms shown to the right are present in very small amounts. Potential to participate in formation of hydrogen bonds is shown by the arrows: hydrogen bond donors are shown by arrows directed away from the atom and acceptors are shown by arrows directed towards the atom.
Figure 3. Conformations of nucleotides. (a) Torsion angle notation (IUPAC definitions) for a polynucleotide. A conventional representation showing the torsion angles relative to atom number of the nucleotide. See Table for a complete description of the atoms defining each angle. (b) Representation of puckering modes of furanose sugar. Three twist (T) forms are shown in which three ring atoms (C4′, O4′, C1′) are planar and the other two (C2′, C3′) lie on opposite sides of this plane. ‘Base’ refers to any purine or pyrimidine base. (c) Anti and syn conformations of the glycosidic bonds for a purine or pyrimidine base. The arrow indicates which base atoms lie above the furanose sugar ring. For purine nucleotides: R1 = H or OH; R2 = NH2 or O; R3 = H or double bond to C6′; R4 = H or NH2. For pyrimidine nucleotides: R1 = H or OH; R2 = H or double bond to C4; R3 = NH2 or O; R4 = H or CH3. (d) Preferred nucleotide conformations at C4′–C5′ and C3′–O3′. The structures show synclinal (sc) and antiperiplanar (ap) rotamers of the C4′–C5′ bond and the typical antiperiplanar/anticlinal (ap/−ac) conformation of the C3′–O3′ bond.
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Further Reading

Berg JM, Tymoczko JL and Stryer L (2012) Biochemistry, 7th edn. Basingstoke, UK: WH Freeman.

Blackburn GM and Gait MJ (1996) Nucleic Acids in Chemistry and Biology, 2nd edn. Oxford, UK: Oxford University Press.

Blackburn GM, Gait MJ, Loakes D and Williams DM (2006) Nucleic acids in chemistry and biology, 3rd edn. Cambridge, UK: Royal Society of Chemistry.

Diekmann S (1989) Definitions and nomenclature of nucleic acid structure parameters. EMBO Journal 8: 1–4.

Herdewijn P (2008) Modified Nucleosides. Biochemistry, Biotechnology and Medicine. Weinheim, Germany: Wiley‐VCH Verlag GmbH & Co. KGaA. Doi: 10.1002/9783527623112.index

Kornberg A and Baker TA (1992) DNA Replication, 2nd edn. New York: Freeman.

Neidle S (1999) Oxford Handbook of Nucleic Acid Structure. Oxford, UK: Oxford University Press.

Neidle S (2002) Nucleic Acid Structure and Recognition. Oxford, UK: Oxford University Press.

Nelson DL and Cox MM (2013) Lehninger's Principles of Biochemistry, 6th edn. New York: WH Freeman.

Saenger W (1984) Principles of Nucleic Acid Structure. New York: Springer‐Verlag.

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Bowater, Richard P, and Gates, Andrew J(Feb 2015) Nucleotides: Structure and Properties. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001333.pub3]