Nucleotide

Nucleotide

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.

see also DNA; DNA Polymerase; Replication; RNA; RNA Polymerases.

Fred Perrino

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.