Effect of dietary change on the rates of synthesis and degradation of rat liver fatty acid synthetase

Investigations were carried out to determine whether diet-induced changes in the level of rat liver fatty acid synthetase are due to changes in the rate of synthesis or degradation of this enzyme. Assays for radioactivity in fatty acid synthetase were carried out through isolation of the enzyme by a standard purification procedure or by immunoprecipitation with antiserum prepared specifically against rat liver fatty acid synthetase. Studies on the incorporation of radioactive leucine into the fatty acid synthetase during steady-state conditions showed that the relative rate of synthesis of this enzyme was decreased to one-fifth the normal value in the fasted state and increased to 14.3 times the normal value in rats refed a fat-free diet. Studies on the degradation of the fatty acid synthetase, reported as half-life of the enzyme, yielded identical values, 69 hr, for normal animals, as well as for animals refed a fat-free diet. The rates of synthesis of enzyme ( k s ) calculated from these half-life values and the enzyme content present in the liver in a given nutritional state agreed well with the relative rates of synthesis. On the basis of these results it is concluded that changes in the level of liver fatty acid synthetase which are diet induced are due primarily to changes in the rate of synthesis rather than degradation of this enzyme. However, transient changes in the rate of degradation may also be important during the transition period, particularly in the case of fasting.