Defects of tetrahydrobiopterin synthesis and their possible relationship to a disorder of purine metabolism (the Lesch-Nyhan syndrome)

摘要: The metabolic pathways of pterin de novo synthesis, interconversion and salvage which lead to the tetrahydrobiopterin cofactor phenylalanine 4-monooxygenase, tyrosine 2-monooxygenase tryptophan 5-monooxygenase are reviewed data on enzymes catalyze individual steps presented. Analogies drawn between inborn errors production Lesch-Nyhan syndrome, in purine is deficient, used as a basis for hypothesis that neurological manifestations syndrome due neurotransmitter imbalance stems from an aromatic amino acid monooxygenase activities themselves impaired biosynthesis. latter arises because, absence hypoxanthine phosphoribosyltransferase catalyzed pathway, supply GTP cyclohydrolase reaction, first reaction synthesis reduced. It proposed different monooxygenases differentially affected by this constrained production. those most directly related quantal cerebral neurotransmitters dopamine, norepinephrine 5-hydroxytryptamine whereas liver 4-monooxygenase activity not overtly impaired. results lines research support concept cited, direct evidence selective reduction dopamine basal ganglia patients with syndrome. lack GMP functions, other than its role accounts features do occur when only deficient synthesis.