Human purine metabolism: some recent advances and relationships with immunodeficiency.

Studies of human purine metabolism began some 200 years ago with Scheele's identification of uric acid as a constituent of a renal calculus' and Wollaston's demonstration of urate in a tophus from his own ear.2 Just as these were among the earliest experiments in the new science of biochemistry, so Garrod's (1854)3 thread test must rank as the first assay in what we now call the discipline of clinical chemistry. Seegmiller's discovery, 15 years ago, that the severe purine overproduction and gout observed in boys with Lesch-Nyhan syndrome resulted from a specific defect of the purine salvage enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT)4 led to what has been described as the 'purine revolution' and was soon followed by the identification of other inborn errors of metabolism associated with primary purine overproduction and gout. Oxypurine and deoxypurine bases, nucleosides, and nucleotides do, however, have much wider physiological importance as intermediates in energy metabolism, components of coenzymes, vasoactive and neurotransmitter substances, mediators of hormonal action, and as the building blocks for transmitters of genetic information (DNA and RNA). Most recently interest has been focused on the role of purines, and especially deoxypurines, in the regulation of immune responses.