Purine Synthesis and Salvage in Brain and Liver

Abstract

Previous work in which we measured the specific activities of amidophosphoribosyltransferase (PRPP-At; EC 2.4.2.14) and hypo-xanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8) in the brains of rats at different ages suggested that the HPRT-catalysed purine salvage pathway became more important relative to the purine de novo synthesis pathway after the main bursts of neuroblast and neuroglial proliferation.¹ This interpretation involves the assumption that changes in the specific activity of PRPP-At, which catalyses the first and presumably ratelimiting reaction on the purine de novo synthesis pathway, are a valid measure of changes in the flow of metabolites along the whole pathway. The evidence² that the cyclic nucleotides (cAMP and cGMP) have important second messenger functions in the central nervous system, some of which are related to post-synaptic neurotransmission, and which presumably become more important as neuronal function increases, suggested to us that HPRT might have a specific function in maintaining the supply of a neuropharmacologically important low molecular weight purine derivative which could be cGMP. We also suggested that a failure of this mechanism might be responsible for the functional disorders of the Lesch-Nyhan syndrome³.