Regulation of the activity of branched-chain 2-oxo acid dehydrogenase (BCODH) complex by binding BCODH kinase.
Branched-chain 2-oxo acid dehydrogenase (BCODH) kinase is responsible for inactivation of BCODH complex by phosphorylation of the complex. Activity of the kinase towards its substrate, the E1 component of the BCODH complex, is known dependent upon binding of the kinase to the E2 component. The possible existence as well as importance of unbound mitochondrial BCODH kinase has been largely ignored in previous studies. Evidence is presented here for the existence of free and bound BCODH kinase in the matrix space of rat liver mitochondria. Furthermore, in female rats, in which diurnal variations in liver BCODH complex and kinase activities occur, the amount of the kinase bound to the complex changes between morning and evening without a change in total kinase protein. Activity of the kinase correlates with the amount of bound rather than total kinase protein, suggesting only the bound form is active. Changes in amount of kinase bound and therefore active appear responsible for diurnal variation in BCODH complex activity in the female rat. We propose that change in the amount of bound BCODH kinase is a key feature of a novel regulatory mechanism for determining the activity state of the BCODH complex.
Department of Sports Medicine, Graduate School of Medicine, Nagoya University, Nagoya 464-8601, Japan.
M
M
Obayashi
Y
Y
Sato
R A
RA
Harris
Y
Y
Shimomura
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm; D004789:Enzyme Activation; D005260:Female; D015151:Immunoblotting; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000597:Amino Acids, Branched-Chain; D009097:Multienzyme Complexes; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D011494:Protein Kinases; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase