CHAPTER 7 - PURINE BIOSYNTHESIS DE NOVO

Abstract

This chapter presents purine biosynthesis de novo. The synthesis of purines from nonpurine precursors is one of the oldest areas of biochemistry. Evidence for the existence of this process became available about 150 years ago, and it has been explicitly studied for some 80–90 years. It was not until about 1960, however, that the enzymatic reactions of purine biosynthesis de novo were identified, and this pathway is still an area of current research. The existence of a purine biosynthetic pathway in mammals was established through the use of purine-free diets. This chapter also discusses the early studies that contributed to an understanding of the site of uric acid biosynthesis and led to several hypothetical reaction schemes. In 1877, several investigators showed that the feeding of urea, amino acids, or ammonium salts to mammals led to an increase in the excretion of urea, the feeding of these compounds to birds resulted instead in an increased excretion of uric acid. In 1886, Minkowski showed that hepatectomized birds did not synthesize uric acid from such precursors, and because urinary lactate was elevated in such birds, he suggested that uric acid was synthesized from lactate and ammonia.