Acute alloxan diabetes alters the activity but not the total quantity of acetyl CoA carboxylase in rat liver.
Alloxan diabetes has repeatedly been shown to reduce lipogenesis in rat liver concomitant with decreased activity of acetyl CoA carboxylase. This and other observations led to the deduction that insulin is required for the synthesis of acetyl CoA carboxylase even though the actual amount of enzyme was not measured. We have developed methods to determine the quantity of acetyl CoA carboxylase in crude tissue extracts with which we have reexamined the role of insulin in regulating the amount of the enzyme in liver of acute (3-d) alloxan diabetic rats. The results show that although there was a decrease in the quantity of the active cytoplasmic form of acetyl CoA carboxylase in the liver of alloxan diabetic rats, there was a corresponding increase in the quantity of relatively inactive forms of the enzyme associated with mitochondria. Thus, the total amount of enzyme was minimally affected by the diabetic state. Instead, the results indicate that decreased acetyl CoA carboxylase activity in liver of the diabetic rats was attributable to a shift in the subcellular distribution of the enzyme from the active cytoplasmic to inactive mitochondrial forms. We have shown previously that subcellular distribution of the enzyme is dietary dependent. Results of this study implicate insulin in the mobilization and activation of mitochondrial acetyl CoA carboxylase.
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D007328:Insulin / Q000494:pharmacology; D008025:Ligases / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D008055:Lipids; D008025:Ligases; D000103:Acetyl-CoA Carboxylase