title: Purine synthesis de novo and salvage in hypoxanthine phosphoribosyltransferase-deficient mice.
abstract: Extreme degrees of hypoxanthine phosphoribosyltransferase (HPRT) deficiency in man are associated with gross sex-linked neurological dysfunction, gout and urinary stones (the Lesch-Nyhan or 'complete HPRT-deficiency' syndrome). The less severe degrees of enzyme deficiency (sex-linked recessive gout and/or urolithiasis or the 'partial HPRT-deficiency' syndrome) may be associated with minor neurological manifestations. Whole body purine synthesis de novo is accelerated in both these groups of patients. A strain of mice with an experimentally produced mutation at the HPRT locus showed some residual 'apparent HPRT activity' in brain, liver, testicular, splenic, kidney and ovarian tissues but not in erythrocyte haemolysates. The mutation removes exons 1 and 2 of the coding region of the gene together with the promotor and about 10 kb of upstream sequence from the gene. It is therefore possible that the observed 'apparent HPRT activity' in these mice is due to the operation of an alternative metabolic pathway. Purine synthesis de novo was markedly accelerated in their brain, testicular, splenic and kidney tissues. It was not accelerated in the liver tissue of male mice hemizygous for the mutation and the degree of acceleration in the female homozygotes only just reached statistical significance at the p = 0.02 level. This observation casts doubt on the importance of modulations in the rate of hepatic purine synthesis de novo as a mechanism for maintaining a steady supply of purines for translocation to other organs.
authors.affiliation: Clinical Research Centre, Harrow, UK.
authors.forename: J
authors.initials: J
authors.lastname: Allsop
authors.forename: R W
authors.initials: RW
authors.lastname: Watts
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D005260:Female; D006066:Gonads / Q000201:enzymology; D006720:Homozygote; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D007926:Lesch-Nyhan Syndrome / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D011687:Purines / Q000378:metabolism*; D013154:Spleen / Q000201:enzymology
chemical_list: D011687:Purines; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase