Regulation of branched-chain amino acid catabolism: nutritional and hormonal regulation of activity and expression of the branched-chain alpha-keto acid dehydrogenase kinase.
Branched-chain alpha-keto acid dehydrogenase kinase is responsible for the inactivation and phosphorylation of the branched-chain alpha-keto acid dehydrogenase complex, the enzyme that catalyses the committed step of branched-chain amino acid catabolism. The activity of the branched-chain alpha-keto acid dehydrogenase complex is inversely correlated with kinase activity, suggesting that the relative activity of the kinase is the primary regulator of the activity of the complex. It has been shown that kinase activity and expression are affected by nutritional states imposed by low-protein diet feeding, starvation, diabetes, and exercise. Evidence has also been presented that certain hormones, particularly insulin, glucocorticoid, thyroid hormone and female sex hormones, affect the activity and expression of the kinase. The findings indicate that nutritional and hormonal control of the activity and expression of branched-chain alpha-keto acid dehydrogenase kinase provides an important means of control of the activity of the branched-chain alpha-keto acid dehydrogenase complex, with inactivation serving to conserve branched-chain amino acids for protein synthesis in some situations and activation serving to provide carbon for gluconeogenesis in others.
Shimomura
Y
Y
Department of Bioscience, Nagoya Institute of Technology, Nagoya, Japan. shimo@ks.nitech.ac.jp
Obayashi
M
M
Murakami
T
T
Harris
R A
RA
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D018753:Diet, Protein-Restricted; D015536:Down-Regulation; D015444:Exercise / Q000502:physiology; D015870:Gene Expression; D006728:Hormones / Q000502:physiology; D006801:Humans; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D013217:Starvation / Q000201:enzymology
D000597:Amino Acids, Branched-Chain; D006728:Hormones; D009097:Multienzyme Complexes; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D011494:Protein Kinases; C035627:(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase