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Alpha-Keto Acid Dehydrogenase Complexes pp 17–32Cite as

Probing the active site of mammalian pyruvate dehydrogenase

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Abstract

The pyruvate dehydrogenase (E1) is the first catalytic component of the multienzyme pyruvate dehydrogenase complex (PDC). El catalyzes the two partial reactions: the thiamin pyrophosphate (TPP)-dependent decarboxylation of pyruvic acid to 2-hydroxyethylidene-TPP (HETPP) [Eq. 1] and reductive acetylation of lipoic acid residues covalently linked to the second catalytic component — dihydrolipoamide acetyltransferase (E2) [Eq. 2] (Reed, 1974):

$$C{H_3}COC{O_2} - + E{1_ - }TPP \to C{H_3}C\left( {OH} \right) = TPP - E1 + C{O_2}$$
([1])
$$C{H_3}C\left( {OH} \right) = TPP - E1 + E2 - lipoates\left( {{S_2}} \right) \to ETPP + E2 - lipoate\left( {SH} \right)SCOC{H_3}$$
(2)

Mammalian E1 is a heterotetramer (α[2]β2) containing two 41 kDa α subunits and two kDa β subunits. The role of individual subunits is not clear. It was proposed that E1α can catalyze the first partial reaction and E1β the second (Roche and Reed, 1972). E1α is thought to be involved in TPP binding as it contains TPP motif found by sequence comparison of several TPP requiring enzymes (Hawkins et al., 1989). Recent evidence indicates that both subunits are involved in TPP binding (Robinson and Chun, 1993; Ali et al., 1995; Korotchkina et al., 1995).

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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA

    L. G. Korotchkina, M. S. Ali & M. S. Patel

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  1. L. G. Korotchkina
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  2. M. S. Ali
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  3. M. S. Patel
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Editors and Affiliations

  1. Department of Biochemistry School of Medicine and Biomedical Sciences, State University of New York, 140 Farber Hall 3435 Main Street, 14214, Buffalo, New York, USA

    Mulchand S. Patel

  2. Department of Biochemistry, Kansas State University, 104 Willard Hall, 66506, Manhattan, KS, USA

    Thomas E. Roche

  3. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, 46202, Indianapolis, IN, USA

    Robert A. Harris

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© 1996 Birkhäuser Verlag Basel/Switzerland

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Korotchkina, L.G., Ali, M.S., Patel, M.S. (1996). Probing the active site of mammalian pyruvate dehydrogenase. In: Patel, M.S., Roche, T.E., Harris, R.A. (eds) Alpha-Keto Acid Dehydrogenase Complexes. MCBU Molecular and Cell Biology Updates. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-8981-0_2

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