Nutritional regulation of the protein kinases responsible for the phosphorylation of the alpha-ketoacid dehydrogenase complexes.
The branched-chain alpha-ketoacid dehydrogenase (BCKDH) and pyruvate dehydrogenase (PDH) complexes are regulated by phosphorylation cycles catalyzed by complex-specific protein kinases and phosphoprotein phosphatases. Molecular cloning of these mitochondrial protein kinases has established a new family of protein kinases in eukaryotes that appears related by primary sequence to the histidine protein kinase family of prokaryotes. Changes in the activities of both kinases that are stable, i.e., not caused directly by allosteric effectors, correlate inversely with the changes in the activity states of the complexes that occur in different nutritional states. For example, BCKDH kinase activity is increased and the BCKDH complex activity state is decreased in rats fed diets deficient in protein. The increase in BCKDH kinase activity is due to an increase in the amount of BCKDH kinase protein bound to the BCKDH complex. The message level for BCKDH kinase also increases in the liver of rats starved for protein, suggesting a pretranslational mechanism exists for the long-term regulation of BCKDH kinase. Starvation and high-fat feeding cause a stable increase in PDH kinase activity and a corresponding decrease in activity state of the PDH complex. The mechanism responsible has not been defined.
Harris
R A
RA
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202-5122, USA.
Popov
K M
KM
Zhao
Y
Y
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D004032:Diet; D015971:Gene Expression Regulation, Enzymologic; D007658:Ketone Oxidoreductases / Q000235:genetics / Q000502:physiology*; D009097:Multienzyme Complexes / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics / Q000502:physiology*
D009097:Multienzyme Complexes; D011768:Pyruvate Dehydrogenase Complex; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)