Congenital lactic acidosis: Evaluation of the properties of the A199T natural variant of human pyruvate dehydrogenase E1 alpha by in vitro mutation

One cause of congenital lactic acidosis is a mutation in the E1 alpha -subu nit of the pyruvate dehydrogenase multienzyme complex. Little is known abou t the consequences of these mutations at the enzymatic level. Here we study the A199T mutation by expressing the protein in Escherichia coil. The spec ific activity is 25% of normal and the K-m for pyruvate is elevated by 10-f old. Inhibitors of lactate dehydrogenase might be a useful therapy for pati ents with such mutations. (C) 2001 Academic Press.