Purine Synthesis and Salvage in Brain and Liver
Previous work in which we measured the specific activities of amidophosphoribosyltransferase (PRPP-At; EC 184.108.40.206) and hypo-xanthine phosphoribosyltransferase (HPRT; EC 220.127.116.11) 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.
KeywordsCyclic Nucleotide Synthesis Pathway Silver Nitrate Solution Purine Synthesis Adenine Phosphoribosyltransferase
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