Lesch-Nyhan Syndrome: Altered Kinetic Properties of Mutant Enzyme

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Science  19 Feb 1971:
Vol. 171, Issue 3972, pp. 689-691
DOI: 10.1126/science.171.3972.689


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.