Acetyl coenzyme A carboxylase. The roles of synthesis and degradation in regulation of enzyme levels in rat liver.

The roles of synthesis and degradation in the regulation of acetyl coenzyme A carboxylase levels in rat liver following fasting and fat-free feeding have been studied. Antibodies prepared to homogeneous chicken liver acetyl-CoA carboxylase were shown to cross-react with rat liver acetyl-CoA carboxylase. Enzyme from both species was totally inactivated as well as precipitated by this antibody preparation. Furthermore, quantitative precipitin curves and equivalence point determinations indicated that enzymes from the two species were precipitated in equal quantity by antibody and that the two enzymes had identical turnover numbers. It was also shown that disaggregated, aggregated, and palmitylCoA-treated enzyme were all equally precipitated by antibody. Immunological analysis of crude homogenates of rat liver from animals treated with different diets, which had specific activities for acetyl-CoA carboxylase varying over Z-fold indicated that there was a constant amount of immunologically precipitable enzyme per unit of enzyme activity. The changes in acetyl-CoA carboxylase activity measured after dietary alteration result from changes in the enzyme content of liver rather than from activation or inhibition of preformed enzyme. The relative rates of acetyl-CoA carboxylase synthesis were determined by quantitative precipitation of the enzyme by antibody after pulse labeling with 3H-leucine. There was a Sto lo-fold increase in the rate of enzyme synthesis after fat-free feeding of previously fasted rats. The rate of degradation of acetyl-CoA carboxylase in rats fed a fat-free diet was found to be &st order with a tx of approximately 48 hours, whereas in fasted rats a tx of 18 hours was obtained. In rats fed a 12% fat diet the rate of acetyl-CoA carboxylase degradation was similar to that found in animals fed a fatfree diet, whereas the rate of synthesis was diminished, thus suggesting that independent factors regulate the rates of