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One cause of congenital lactic acidosis is a mutation in the E1α-subunit of the pyruvate dehydrogenase multienzyme complex. Little is known about the consequences of these mutations at the enzymatic level. Here we study the A199T mutation by expressing the protein in Escherichia coli. The specific activity is 25% of normal and the K m for pyruvate is elevated by 10-fold. Inhibitors of lactate...
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