Nucleosides contain a sugar linked to a nitrogen-containing base. The physiologically important bases, purines and pyrimidines, have ring structures (Figure 1). These structures are bound to ribose or 2-deoxyribose to complete the nucleoside. When inorganic phosphate is added to the nucleoside, a nucleotide is formed. Nucleosides and nucleotides form the backbone for RNA and DNA, as well as a variety of coenzymes and regulatory molecules of physiologic importance (eg, NAD+, NADP+, and ATP; Table 1). Nucleic acids in the diet are digested and their constituent purines and pyrimidines absorbed, but most of the purines and pyrimidines are synthesized from amino acids, principally in the liver. The nucleotides and RNA and DNA are then synthesized. RNA is in dynamic equilibrium with the amino acid pool, but DNA, once formed, is metabolically stable throughout life. The purines and pyrimidines released by the breakdown of nucleotides may be reused or catabolized. Minor amounts are excreted unchanged in the urine.
Fig1. Principal physiologically important purines and pyrimidines. Purine and pyrimidine structures are shown next to representative molecules from each group. Oxypurines and oxypyrimidines may form enol derivatives (hydroxypurines and hydroxypyrimidines) by migration of hydrogen to the oxygen substituents.
Table1. Purine- and pyrimidine-containing compounds.
The pyrimidines are catabolized to the β-amino acids, β-alanine, and β-aminoisobutyrate. These amino acids have their amino group on β-carbon, rather than the α-carbon typical to physiologically active amino acids. Because β-aminoisobutyrate is a product of thymine degradation, it can serve as a measure of DNA turnover. The β-amino acids are further degraded to CO2 and NH3 .
Uric acid is formed by the breakdown of purines and by direct synthesis from 5-phosphoribosyl pyrophosphate (5-PRPP) and glutamine (Figure 2). In humans, uric acid is excreted in the urine, but in other mammals, uric acid is further oxidized to allantoin before excretion. The normal blood uric acid level in humans is approximately 4 mg/dL (0.24 mmol/L). In the kidney, uric acid is filtered, reabsorbed, and secreted. Normally, 98% of the filtered uric acid is reabsorbed and the remaining 2% makes up approximately 20% of the amount excreted. The remaining 80% comes from the tubular secretion. The uric acid excretion on a purine-free diet is about 0.5 g/24 h and on a regular diet about 1 g/24 h. Excess uric acid in the blood or urine is a characteristic of gout.
Fig2. Synthesis and breakdown of uric acid. Adenosine is converted to hypoxanthine, which is then converted to xanthine, and xanthine is converted to uric acid. The latter two reactions are both catalyzed by xanthine oxidase. Guanosine is converted directly to xanthine, while 5PRPP and glutamine can be converted to uric acid.
