Role of ATP in the regulation of branched-chain alpha-keto acid dehydrogenase activity in liver and muscle mitochondria of fed, fasted, and diabetic rats.
The activity of branched-chain alpha-keto acid (BCKA) dehydrogenase was increased after preincubation of liver and muscle mitochondria of control rats. Preincubation depleted mitochondrial ATP. Addition of ATP prevented the activation of BCKA dehydrogenase as well as reversed the activity of a fully activated enzyme to normal. Inhibition of phosphatase blocked the activation of BCKA dehydrogenase. There was a small or no increase in BCKA dehydrogenase activity when mitochondria from tissues of fasted, diabetic, and clofibrate-treated rats were preincubated. In fasted and diabetic rats, ATP was either less effective or failed to reverse the increased dehydrogenase activity in preincubated mitochondria. The concentration of ATP in liver and muscle mitochondria of diabetic rats was approximately one-half that of the control rats. We conclude that (a) in the fed state approximately 30-40% of BCKA dehydrogenase exists in the active form. The enzyme can be fully activated by preincubation of mitochondria which causes the depletion of ATP. Phosphatase is necessary for this activation. (b) In fasted, diabetic, and clofibrate-treated rats, approximately 70-100% of the enzyme exists in the active form which may be related to the mitochondrial depletion of ATP in vivo, and (c) while ATP can reverse the activation in control rats, it fails to do so in diabetic rats suggesting that other metabolic alterations may be involved in the regulation of BCKA dehydrogenase in diabetes.
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005215:Fasting; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D008931:Mitochondria, Muscle / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains
D009097:Multienzyme Complexes; D000255:Adenosine Triphosphate; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)