Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 318153
Title Structural basis for the dysfunctioning of human 2-oxo acid dehydrogenase complexes
Author(s) Hengeveld, A.F.; Kok, A. de
Source Current Medicinal Chemistry 9 (2002). - ISSN 0929-8673 - p. 499 - 520.
Department(s) Biochemistry
Publication type Refereed Article in a scientific journal
Publication year 2002
Abstract 2-oxo acid dehydrogenase complexes are a ubiquitous family of multienzyme systems that catalyse the oxidative decarboxylation of various 2-oxo acid substrates. They play a key role in the primary energy metabolism: in glycolysis (pyruvate dehydrogenase complex), the citric acid cycle (2-oxoglutarate dehydrogenase complex) and in amino acid catabolism (branched-chain 2-oxo acid dehydrogenase complex). Malfunctioning of any of these complexes leads to a broad variety of clinical manifestations. Deficiency of the pyruvate dehydrogenase complex predominantly leads to lactic acidosis combined with impairment of neurological function and/or delayed growth and development. Maple urine disease is an inborn metabolic error caused by dysfunction of the branched-chain 2-oxo acid dehydrogenase complex. An association between both Alzheimer disease and Parkinson's disease and the 2-oxoglutarate dehydrogenase gene has been reported. Currently a wealth of both genetic and structural information is available. Three-dimensional structures of three components of the complex are presently available: of the pyruvate dehydrogenase component (E1), of the dihydrolipoyl acyltransferase component (E2) and of the lipoamide dehydrogenase component (E3). Moreover, detailed information on the reaction mechanism, regulation and the interactions between the different components of the complex is now at hand. Although only one of the structures is of human origin (E1b), model building by homology modelling allows us to investigate the causes of dysfunction. In this review we have combined this knowledge to gain more insight into the structural basis of the dysfunctioning of the 2-oxo acid dehydrogenase complexes.
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