Fatty Acid Synthetase of Developing Brain and Liver

Abstract

Abstract Immunochemical techniques have been utilized to study the content, synthesis, and degradation of the fatty acid synthetase in liver and brain during development and in various nutritional states. The distinctive changes in synthetase activity during development of both tissues are related entirely to changes in content of enzyme. During fasting and fat-free feeding, in contrast to the lack of change in synthetase activity of brain, there are dramatic alterations in hepatic activity. These changes are related entirely to changes in content of enzyme in liver. During development of brain the rate of synthesis of the enzyme decreases. In developing liver, when synthetase activity rises at the time of weaning, there is a marked acceleration of synthesis of enzyme. During fasting, when hepatic synthetase concentration falls drastically, there is a considerable reduction in synthesis of enzyme, and when animals are refed a fat-free diet, a remarkable increase in enzyme synthesis occurs, confirming earlier reports. The rate of fatty acid synthetase degradation in brain of adult animals differs considerably from that in liver; the half-lives are 6.4 and 2.8 days, respectively. In young suckling animals the rate of degradation of the enzyme in brain is markedly accelerated (t1/2 = 1.9 days), whereas in liver there is little change (t1/2 = 2.3 days). The most profound change in degradation of synthetase in liver occurs during fasting when the t1/2 decreases to 18 hours. No changes were observed in degradation in brain during fasting or fat-free feeding. Rate constants for synthesis and degradation of fatty acid synthetase in liver and brain during development and in the various nutritional states were derived; these quantitatively accounted for the differences in content of the enzyme in these tissues. In developing liver the dramatic elevation in synthetase content apparent after weaning is associated with an acceleration of enzyme synthesis but no change in rate of enzyme degradation. The changes in enzyme content during development of brain are accompanied by alterations in the rates of synthesis and degradation of fatty acid synthetase. Both processes are more rapid in the brain of the young suckling animal than in the mature animal. These observations represent the first direct measurements of rates of synthesis and degradation of an enzyme in mammalian brain.