Introduction to Molecular Biology: From Cells to Atoms - Anthony Rees, Michael Sternberg 2002

Nucleic Acids and Genes
Primary Structure of Nucleic Acids

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Fig. 17.1

Nucleic Acids—deoxyribonucleic acid (DNA) and ribonucleic acid (RNA)—are polymeric macromolecules responsible for storing and transferring Genetic information. They are built from monomeric units called NUCLEOTIDES.

A nucleotide consists of three parts: a nitrogenous base, a monosaccharide (sugar), and one or more phosphate groups. In DNA and RNA, a single phosphate group is attached to each nucleotide. A nucleoside is a nucleotide lacking the phosphate group(s); thus, nucleotides are essentially phosphoric esters of nucleosides.

The sugar component of a nucleotide is a pentose, which can exist in one of two forms: ß-D-ribose or ß-D-2-deoxyribose. The structural difference between them is that the hydroxyl (—OH) group at the 2'-carbon atom of ribose is replaced by a hydrogen atom in deoxyribose. Nucleotides containing ribose are called ribonucleotides and serve as the monomer units of RNA, whereas those containing deoxyribose are deoxyribonucleotides, which make up DNA. Nitrogenous bases are derivatives of one of two parent compounds: purine or pyrimidine. Nucleic acids primarily contain two purine derivatives—adenine (designated as A) and guanine (G)—and three pyrimidine derivatives—cytosine (C), thymine (T), and uracil (U). Ribonucleotides incorporate the bases A, G, C, and U, while deoxyribonucleotides incorporate A, G, C, and T. The base is attached to the sugar via a ß-N-glycosidic bond linking the C1' atom of the pentose to the N1 atom of a pyrimidine or the N9 atom of a purine.

One, two, or three phosphate groups may be linked via an ester bond to the 5'-carbon of the pentose. Accordingly, these nucleotides are termed nucleoside 5'-mono-, nucleoside 5'-di-, and nucleoside 5'-triphosphates, abbreviated as XMP, XDP, and XTP, respectively, where X represents the nitrogenous base. The Greek letters α, ß, and γ are used to designate the three different positions of the phosphate groups. At physiological pH values (close to 7), the bases are uncharged; however, the one, two, or three phosphate groups in XMP, XDP, and XTP are acidic and bear two, three, or four negative charges, respectively.

The nomenclature of the bases, their nucleotides (in the 5'-monophosphate form), and nucleosides is summarized in Table 17.1. A prefix before the nucleotide abbreviation indicates that the sugar component is deoxyribose.

Adenosine triphosphate (ATP) is the primary energy currency in all Cells. Each of the three phosphate groups can be cleaved by Hydrolysis to yield orthophosphate (HPO^2-₄), commonly referred to as inorganic phosphate and denoted as P_i. This hydrolysis is accompanied by a decrease in Free energy (Chap. 7):

Fig. 17.2

Table 17.1. Nomenclature of Bases

Within The Cell, ATP, ADP, and AMP typically exist as complexes with magnesium or manganese ions (Mg²⁺ or Mn²⁺). RNA and DΝΑ are constructed from covalently linked ribonucleotide or deoxyribonucleotide units, respectively, forming polynucleotide chains. These units are joined together by phosphodiester bridges linking the 5'-hydroxyl group of one nucleotide to the 3'-hydroxyl group of the next. This creates a regular backbone of phosphate—sugar—phosphate—sugar and so forth. The various bases are attached to the sugars in a manner analogous to side chains in Proteins. The linear sequence of bases along the chain is referred to as the Primary Structure of the nucleic acid (cf. proteins, Chap. 6). The polynucleotide chain exhibits polarity, and by convention, The base sequence is read in the 5'- to 3'-direction of the pentose carbon atoms. The first and last nucleotides are said to be located at the 5'- and 3'-ends of the chain, respectively.

17.3.

Simplified notations are often used to represent the Chemical Structure of a polynucleotide. One can simply specify the base sequence starting from the 5'-end of the molecule, for example, ACG; alternatively, the letter 'p' can be used to indicate the positions of phosphate groups, such as pApCpG. The Nature of the sugar is denoted by the prefixes r (ribose) and d (deoxyribose), e.g., dAdCdG. Schematic representations are also employed, in which a vertical line denotes the pentose, with the letter corresponding to a given base attached to it. The phosphate group linking the sugars is depicted by a slanted line containing the letter P:

Fig. 17.4