| Nucleotides are intimately involved in the normal physiology of cells. As nucleoside triphosphates, they constitute the currency of energy within cells. In other forms they participate at multiple levels in intermediary metabolism, from nucleotide and macromolecule biosynthesis to the biosynthesis of complex carbohydrates and the regulation of metabolism. Because nucleotides are involved in so many levels of metabolism they are important targets for chemotherapeutic agents used in treatment of microbial and parasitic infections and cancer.
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| This chapter will discuss the structure and metabolism of the two classes of nucleotides, purines and pyrimidines. The metabolic pathways are divided into four sections:
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- de novo synthesis of nucleotides from basic metabolites, which provides a source of nucleotides from basic building blocks in growing cells;
- salvage pathways that recycle preformed bases and nucleosides and provide an adequate supply of nucleotides in cells at rest;
- catabolic pathways for excretion of nucleotide degradation products, a process that is essential to limit the accumulation of toxic levels of nucleotides within cells;
- biosynthetic pathways for conversion of the ribonucleotides into the deoxyribonucleotides, providing precursors for deoxyribonucleic acid (DNA) synthesis.
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| Nucleotides are formed from three components: a nitrogenous base, a five-carbon sugar, and a phosphate moiety. The nitrogenous bases found in nucleic acids belong to one of two heterocyclic groups, either purines or pyrimidines (Fig. 29.1). The major purines of both DNA and ribonucleic acid (RNA) are guanine and adenine.
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| In DNA the major pyrimidines are thymine and cytosine, while in RNA the major pyrimidines are uracil and cytosine; thymine is unique to DNA, and uracil is unique to RNA. When the nitrogenous bases are combined with a five-carbon sugar, they are known as nucleosides. When the nucleosides are phosphorylated, the compounds are known as nucleotides. The phosphate can be attached either at the 5'-position or the 3'-position of ribose, or both. Table 29.1 gives the names and structures of the most important purines and pyrimidines.
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