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Lesch‐Nyhan syndrome and its pathogenesis: Normal nicotinamide‐adenine dinucleotide but reduced ATP concentrations that correlate with reduced poly (ADP‐ribose) synthetase activity in HPRT‐deficient lymphoblasts
Author(s) -
McCreanor G. M.,
Harkness R. A.
Publication year - 1995
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf02436765
Subject(s) - hypoxanthine guanine phosphoribosyltransferase , adenine phosphoribosyltransferase , nicotinamide adenine dinucleotide , nad+ kinase , hypoxanthine , lesch–nyhan syndrome , cofactor , phosphoribosyltransferase , biochemistry , biology , nicotinamide , lymphoblast , ribose , hypoxanthine phosphoribosyltransferase , microbiology and biotechnology , enzyme , purine , cell culture , genetics , gene , mutant
Summary In hypoxanthine (guanine) phosphoribosyltransferase‐ (HPRT; EC 2.4.2.8) deficient lymphoblasts, ATP but not nicotinamide‐adenine dinucleotide coenzyme concentrations are reduced by limited nutrition. Such reduced ATP concentrations are correlated with reduced poly(ADP‐ribose) synthetase (polyADPRT; EC 2.4.2.30) activity; this reduces the breakdown of nicotinamide‐adenine dinucleotide coenzymes and thus explains their normal intracellular concentrations. Since reductions in poly(ADP‐ribose) synthetase activity reduce DNA repair, alterations in DNA could accumulate even in non‐multiplying cells such as neurons, especially in the continuously active ‘respiratory centre’. Our Lesch‐Nyhan patients suffered respiratory deaths between 15 and 20 years of age.