Purine and pyrimidine metabolism

Purines and pyrimidines are essential constituents of animal and plant cells and are contained in various compounds.It is interesting to consider that some of these compounds are very stable, e.g.DNA, while others are rapidly turned over, e.g.ATP.In birds and reptiles uric acid also serves to excrete nitrogen.The aim of this paper is to give a short review of purine and pyrimidine metabolism and to describe in some detail aspects important to the field of nutrition, with emphasis placed on work done in vitro and in man. PurinesThe most important structure in purine biochemistry is the nucleotide consisting of a purine base, ribose or deoxyribose, and phosphoric acid.The most important purine bases are adenine, guanine, hypoxanthine and xanthine.The ribosides of all of them are known to occur in metabolism.Adenine and guanine themselves are usually not found in the tissues of mammals, but free hypoxanthine and xanthine are intermediates in the degradation of purines.Uric acid is a divalent acid, but the second dissociation constant is so small that at around pH 7 only the monobasic salts are formed.These are sparingly soluble in the body fluids.Peters & van Slyke (1946) have calculated a maximum solubility of 6.5 mg/Ioo ml (as uric acid) in plasma.Gout and uric acid nephropathies are due to this low solubility.Nucleosides are pentose-glycosides containing ribose or deoxyribose.Normally the linkage is with atom 9, but nucleosides with atom 3 do occur.Nucleosides are rather soluble in water.Nucleotides are phosphate esters of the pentose in the nucleoside.In mononucleotides the esters are in position 5', in polynucleotides (nucleic acids) phosphate is esterified at position 5' of one and position 3' of the next pentose.The biochemistry of purines has recently been reviewed by Wyngaarden 8z Kelley (1978). Metabolism of endogenous purinesIt has long been known that purines are not essential constituents of food and that ammonia is one of the precursors in purine biosynthesis.Krebs was the first to demonstrate purine synthesis in vitro in liver slices; today the pathway of purine biosynthesis is well elucidated.Three positions of the purine structure come from glycine, all other atoms are delivered from simple donors such as CO,, formyl esters or ammonia.The common end-product of purine synthesis in all vertebrates so far studied is inosinic acid (IMP), the nucleotide of hypoxanthine.One of the key substances of purine biosynthesis therefore is phosphoribosylpyrophosphate