Congenital lactic acidosis: evaluation of the properties of the a199t natural variant of human pyruvate dehydrogenase e1alpha by in vitro mutation

One cause of congenital lactic acidosis is a mutation in the E1 alpha-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 speci...

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Bibliographic Details
Published inMolecular genetics and metabolism Vol. 72; no. 3; p. 269
Main Authors Wu, Y G, Widjaja, S L, Huang, C Y, Li, W, Nixon, P F, Duggleby, R G
Format Journal Article
LanguageEnglish
Published United States 01.03.2001
Subjects
Acidosis, Lactic - congenital
Acidosis, Lactic - genetics
Escherichia coli - genetics
Humans
Mutagenesis
Mutation
Pyruvate Dehydrogenase (Lipoamide)
Pyruvate Dehydrogenase Complex - genetics
Pyruvate Dehydrogenase Complex - metabolism
Transfection
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Summary:One cause of congenital lactic acidosis is a mutation in the E1 alpha-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 dehydrogenase might be a useful therapy for patients with such mutations.
ISSN:1096-7192