Abstract
A series of experiments was performed to test the proposal of others that citrate cleavage enzyme (EC 4.1.3.8) regulates the rate of fatty acid synthesis in rat liver. The results show that, in recovery from fasting, fatty acid synthesis increased markedly without change in citrate cleavage enzyme activity. After the administration of alloxan, fatty acid synthesis decreased prior to any change in citrate cleavage enzyme. Substitution of a high carbohydrate, low fat diet resulted in large increases in citrate cleavage enzyme activity without concomitant change in lipogenesis. The addition of purified citrate cleavage enzyme from rat liver to the fatty acid-synthesizing system from fasted animals did not restore fatty acid synthesis. It was concluded that citrate cleavage enzyme does not play a primary regulatory role in fatty acid synthesis.
Highlights
Refeeding ExperimentsAs noted above, when sequence studies were carried out by fasting rats and measuring fatty acid synthesis and citrate cleavage enzyme at varying time intervals, it was shown that fatty acid synthesis markedly decreased at 12 hours and fell to near zero levels at 24 hours without change in the activity of citrate cleavage enzyme [12]
Experiments with Alloxan Diabetic :lnimalsIt has long been known that fat.ty acid synthesis is greatly decreased in alloxan diabetes [16]
It is widely believed that citrate is the major substrate for fatty acid synthesis in the cell through generation of acetyl-Co.4 in the extramitochondrial compartment via the citrate cleavage enzyme reaction [2, 7, 17, 18]
Summary
LnimalsIt has long been known that fat.ty acid synthesis is greatly decreased in alloxan diabetes [16]. In order to study further the relationship of citrate cleavage enzyme to fatty acid synthesis, these parameters were examined at varying time intervals after the induction of experimental diabetes. The initial level of fatty acid synthesis in the fed control animals was. Three hours after the alloxan injection, lipogenesis had decreased to 2.2 mpmoles per min per g. Fatty acid synthesis continued to decrease slowly until 48 hours, at which time synthesis was barely detectable. Citrate Cleavage Enzyme and Fatty Acid Synthesis
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