Fatty acid synthesis by complex systems The possibility of regulation by microsomes

Abstract

1. 1. Fatty acid synthesis from malonyl-CoA catalyzed by rat-liver microsomal protein does not seem to be due to contamination with enzymes from the particle-free supernatant or mitochondrial fractions. 2. 2. Optimum conditions for the conversion of malonyl-CoA to fatty acids by rat-liver microsomes with respect to substrate concentration, protein concentration, and incubation time were established. The enzyme systems concerned with fatty acid synthesis from malonyl-CoA in the particle-free supernatant fraction were 4–5 times more active than those in the microsomes. 3. 3. Preincubation of the microsomes caused a release of malonyl-CoA decarboxylase (EC 4.1.1.9) but not of fatty acid synthetase. This resulted in a greater conversion of the available malonyl-CoA to fatty acids. 4. 4. The products of synthesis in the supernatant system were free fatty acids bound to protein, whereas the products of the microsomal system were predominantly complex lipids (phospholipid). 5. 5. The predominant fatty acid synthesized from malonyl-CoA by the supernatant fraction was palmitate, and that synthesized by the microsomes was stearate. 6. 6. In the system composed of the supernatant fraction plus microsomes, the fatty acids synthesized were complex lipids (phospholipids), and the pattern of fatty acid synthesis resembled that found in the liver slice. 7. 7. The mechanism of the stimulatory effect of microsomes on fatty acid synthesis by the supernatant fraction is discussed and tentatively localized at the level of acetyl-CoA carboxylation. The stimulation may be due to a release of feedback inhibition.