The pathogenesis of the Lesch-Nyhan syndrome: ATP use is positively related to hypoxanthine supply to hypoxanthine guanine phosphoribosyltransferase.
In order to explain features of severe hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency, the Lesch-Nyhan syndrome, a continuous supply of substrate, hypoxanthine, for the enzyme must be generated. This supply must be increased in association with increased ATP turnover. We have shown that ATP turnover continuously supplies hypoxanthine for recycling by the enzyme HPRT and that this supply increases curvilinearly with increasing ATP turnover. The effects of increasing exercise on ATP turnover were examined using a Latin square experimental design. The outputs of hypoxanthine, xanthine, urate and creatinine were measured. The data were then examined statistically.
Harkness
R A
RA
Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Middlesex, UK.
McCreanor
G M
GM
Greenwood
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000375:Aging / Q000652:urine; D015992:Body Mass Index; D003404:Creatinine / Q000652:urine; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency* / Q000378:metabolism; D007042:Hypoxanthines / Q000378:metabolism* / Q000652:urine; D007700:Kinetics; D007926:Lesch-Nyhan Syndrome / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D014527:Uric Acid / Q000652:urine; D019820:Xanthine; D014970:Xanthines / Q000652:urine
D007042:Hypoxanthines; D014970:Xanthines; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D000255:Adenosine Triphosphate; D003404:Creatinine; D007041:Hypoxanthine Phosphoribosyltransferase