Cases Of Maple Syrup Urine Disease Research Articles

Altered enzyme kinetics in fibroblasts of patients with maple syrup urine disease (MSUD).

MSUD results from an inherited defect in oxidative decarboxylation of branched chain α-keto acids (BCKA). Kinetic data for the BCKA decarboxylation were obtained with cultured fibroblasts of normal individuals and 9 MSUD patients with different clinical pictures. The liberation of 14CO2 from (1-14C) BCKA was determined by a micro-enzyme assay for substrate conc. ranging over three orders of magnitude. Of two kinetically distinct decarboxylase components for each BCKA present in normal controls the one with higher substrate affinity was affected in all cases of MSUD investigated: for α-ketoisocaproate (KIC) the normally hyperbolic substrate curve was changed to sigmoid shape, for α-ketoisovalerate (KIVA) and α-keto-β-methylvalerate (MEVA) this component was not detectable at all. In one patient's cell strain, additionally, the component with lower substrate affinity was altered. Reaction rates of normal and mutant decarboxylases differ widely at low substrate conc. and do not at high conc. of BCKA in 8 cases of MSUD. Kinetic studies of BCKA decarboxylation appear suitable for classification in some cases of MSUD.