Decarboxylation of branched-chain alpha-ketoacids in hepatocytes from alloxan-diabetic rats. The effect of insulin.
The flux through branched-chain alpha-ketoacid dehydrogenase and the activity of the branched-chain alpha-ketoacid dehydrogenase complex were measured in hepatocytes isolated from fed, starved and alloxan diabetic rats. The highest rate of branched-chain alpha-ketoacid oxidation was found in hepatocytes isolated from starved rats, slightly lower in those from fed rats, and significantly lower in diabetic hepatocytes. The amount of the active form of branched-chain alpha-ketoacid dehydrogenase was only slightly diminished in diabetic hepatocytes, whereas the flux through the dehydrogenase was inversely correlated with the rate of endogenous ketogenesis. The same was observed in hepatocytes isolated from starved rats when branched-chain alpha-ketoacid oxidation was measured in the presence of added oleate. In both cases the diminished flux through the dehydrogenase, restored by a short preincubation of hepatocytes with insulin, was paralleled by a decrease of fatty acid-derived ketogenesis. The significance of these findings is discussed in relation to the role of insulin in branched-chain alpha-ketoacid oxidation in liver of diabetic rats.
Sterniczuk
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A
Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
Wałajtys-Rode
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EI
Wojtczak
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AB
D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000818:Animals; D003653:Decarboxylation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D045782:Hemiterpenes; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007651:Keto Acids / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007659:Ketones / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation / Q000378:metabolism
D045782:Hemiterpenes; D007328:Insulin; D007651:Keto Acids; D007659:Ketones; D009097:Multienzyme Complexes; C001505:alpha-ketoisovalerate; C013082:alpha-ketoisocaproic acid; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)