Lesch-Nyhan syndrome: altered kinetic properties of mutant enzyme.
Hypoxanthine-guanine phosphoribosyltransferase is virtually inactive in erythrocytes from patients with the classical Lesch-Nyhan syndrome. In one such patient, activity of this enzyme ranged from 8 to 34 percent of normal in erythrocytes when assayed with a very high concentration of magnesium 5-phosphoribosyl-1-pyrophosphate. In addition, the mutant enzyme exhibited sigmoidal kinetics with this substrate as well as an increased Michaelis constant for both guanine and hypoxanthine. These findings provide the first evidence for genetic heterogeneity within the group of patients with the Lesch-Nyhan syndrome.
D001264:Athetosis / Q000235:genetics; D002648:Child; D002819:Chorea / Q000235:genetics; D003192:Compulsive Behavior; D011756:Diphosphates / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology; D006147:Guanine / Q000378:metabolism; D006801:Humans; D007042:Hypoxanthines / Q000378:metabolism; D008607:Intellectual Disability; D007700:Kinetics; D008297:Male; D008967:Molecular Biology; D009154:Mutation; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000201:enzymology*; D012652:Self Mutilation; D014166:Transferases / Q000097:blood / Q000378:metabolism*; D014527:Uric Acid / Q000097:blood
D011756:Diphosphates; D007042:Hypoxanthines; D014527:Uric Acid; D006147:Guanine; D014166:Transferases