MINI-REVIEW: Short-Term Regulation of the alpha-Ketoglutarate Dehydrogenase Complex by Energy-Linked and Some Other Effectors

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S. Strumilo

Department of Animal Biochemistry, Institute of Biology, University of Bialystok, 15-950 Bialystok, Poland; fax: +4885-745-7302; E-mail: sstrum@uwb.edu.pl

Received September 20, 2004; Revision received November 8, 2004

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The question of regulation of alpha-ketoglutarate dehydrogenase complex (KGDHC) has been considered in the biochemical literature very rarely. Moreover, such information is not usually accurate, especially in biochemical textbooks. From the mini-review of research works published during the last 25 years, the following basic view is clear: a) animal KGDHC is very sensitive to ADP, P_i, and Ca²⁺; b) these positive effectors increase manifold the affinity of KGDHC to alpha-ketoglutarate; c) KGDHC is inhibited by ATP, NADH, and succinyl-CoA; d) the ATP effect is realized in several ways, probably mainly via opposition versus ADP activation; e) NADH, besides inhibiting dihydrolipoamide dehydrogenase component competitively versus NAD⁺, decreases the affinity of alpha-ketoglutarate dehydrogenase to substrate and inactivates it; f) thioredoxin protects KGDHC from self-inactivation during catalysis; g) bacterial and plant KGDHC is activated by AMP instead of ADP. These main effects form the basis of short-term regulation of KGDHC.

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KEY WORDS: alpha-ketoglutarate dehydrogenase, 2-oxoglutarate dehydrogenase, complex, regulation

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