1
Structures of Nucleotide-Related Compounds

1.1 Introduction

The chemistry of purine, pyrimidine, and pyridine nucleobases, nucleosides, and nucleotides constitute one of the oldest topics in biochemistry. In this chapter, the nomenclature and structures of nucleotides are briefly described.

1.2 Nomenclature and Abbreviations of Nucleotide-Related Compounds

The nucleotide nomenclature and abbreviations employed in the text are those used by Henderson and Paterson (1973) in their textbook 'Nucleotide Metabolism - An Introduction'. The terms 'nucleoside' and 'nucleotide' in the strictest sense refer, respectively, to N-glycosides and phosphorylated N-glycosides derived from nucleic acids. However, they are now used in a wider context. N-Ribosides, such as nicotinamide mononucleotide (NMN), are called nucleotides only by extension and analogy, and nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are referred to as dinucleotides. Flavin mononucleotide (FMN) is a step further removed, as it contains ribitol, a pentose alcohol formed by the reduction of ribose, instead of ribose, while flavin adenine dinucleotide (FAD) similarly extends the meaning of dinucleotide. N-Glycosides such as orotidine 5´-monophosphate (OMP) and adenylosuccinate (SAMP) are called nucleotides through their close relationship to the 'true' nucleotides. The terms ribonucleoside and ribonucleotide are used in preference to riboside and ribotides. The IUPAC-IUB Combined Commission on Biochemical Nomenclature has abbreviations and symbols for nucleotides and related compounds. However, as argued by Henderson and Paterson (1973), while they are appropriate for polynucleotides, the distinction between bases and nucleosides is not always immediately obvious, and this has limited their use. The abbreviations used here are more intuitive and better suited to the portrayal of reaction schemes in which the addition or removal of substituent groups occurs.

In Table 1.1, the abbreviations for the major nucleotides, ribo- and deoxyribonucleotides and nucleobases are presented. For readers convenience, the styles used both in this book (style #1) and those recommended by IUPAC (style #2) are shown.

Table 1.1 Nomenclature and abbreviations of purine and pyridine ribo- and deoxyribonucleotides and related compounds.

Two types of symbols are used for nucleoside and nucleobases. Style #1: recommended in Nucleotide Metabolism (Henderson and Paterson 1973). Style #2: recommended by the IUPAC-IUB Commission on Biochemical Nomenclature (1970). In this book, style #1 is adopted.

Abbreviations for ribonucleosides and 2-deoxyribonucleosides are derived from those used for the bases plus those for the ribosyl or 2´-deoxyribosyl groups. Thus AR stands for adenosine and AdR is the abbreviation for deoxyadenosine. In the case of inosine, (hypoxanthine?+?ribose) HR may be possible, but IR is often used. The latter is used in this text.

For nucleotides, the traditional abbreviations based on the term 'nucleoside monophosphate' are used. Thus AMP stands for adenosine monophosphate (adenylate), UMP for uridine monophosphate (uridylate), and NMP for any ribonucleoside monophosphate. Similarly, dAMP stands for deoxyadenosine monophosphate (deoxyadenylate), dUMP for deoxyuridine monophosphate (deoxyuridylate), and dNMP for any deoxyribonucleoside monophosphate. Thymidine monophosphate (thymidylate) often does not have the 'deoxy' prefix in its name, because thymidine is thymine deoxyriboside. However, the symbol including a 'd' is commonly used in biochemistry textbooks, so dTMP is adopted in this article.

1.3 Chemical Structures of Nucleotide-Related Compounds

Studies on purines and pyrimidines began in 1776 when the Swedish pharmacist Carl Wilhelm Scheele isolated uric acid from bladder stones. In 1846, Unger isolated guanine from the guano of Peruvian sea birds. At the end of the nineteenth century, several purines (adenine, xanthine, and hypoxanthine) and pyrimidines (thymine, cytosine, and uracil) were discovered by the German biochemist, Albrecht Kossel who believed they constituted the main part of cell nuclei. In 1874 Friedrich Miescher isolated nuclear material rich in phosphorus which he called 'nuclein'. In the same period, Emil Fischer (1884) elucidated the structures of caffeine and related compounds which he confirmed by chemical synthesis. Further information can be found in a historical survey by Burnstock and Verkhratsky (2012). The pyridine nucleotide, NAD was discovered by the British biochemists Arthur Harden and William John Young in the early twentieth century (Harden and Young 1906).

1.3.1 Purines

A purine is a heterocyclic compound that consists of a pyrimidine ring fused to an imidazole ring. The word, 'purine' ('Purum'?+?'Uricum') was coined by Emil Fischer (1884).

1.3.1.1 Purine Bases

As shown in structure 1 the atoms of the purine ring are numbered in an anticlockwise manner. In plants, there are several naturally occurring purine bases. They include adenine (2) and guanine (3), which are constituents of nucleic acids, and hypoxanthine (4), xanthine (5), and uric acid (6), which are produced as catabolites of adenine and guanine. Purine alkaloids, such as theobromine (3,7-dimethylxanthine) (7), theophylline (1,3-dimethylxanthine) (8), caffeine (1,3,7-trimethylxanthine) (9), and theacrine (1,3,7,9-tetramethyluric acid) (10) are derived from purine nucleotides, as are the major cytokinin plant hormones isopentenyladenine (11), benzyladenine (12), and trans-zeatin (13) (Ashihara et al. 2013).

1.3.1.2 Purine Nucleosides

A nucleoside consists of a nucleobase and a five-carbon sugar (ribose or deoxyribose). Adenosine (14), guanosine (15), inosine (16), and xanthosine (17) are catabolites of purine ribonucleotides and RNA while deoxyadenosine (18) and deoxyguanosine (19) are catabolites of DNA. Cytokinins also occur as ribosides, namely, isopentenyladenine riboside (20), benzyladenine riboside (21), and trans-zeatin riboside (22) (Ashihara et al. 2013).

1.3.1.3 Purine Nucleotides

A nucleotide is composed of a purine base, a sugar moiety (ribose or deoxyribose) and at least one phosphate group. The phosphate group is attached to either the...