Fatty acid biosynthesis VII. Substrate control of chain-length of products synthesised by rat liver fatty acid synthetase

Abstract

1. 1. Gas-liquid and paper chromatography have been used to determine the chain-lengths of fatty acids synthesised by purified rat liver fatty acid synthetase from [1- 14C]acetyl-CoA, [1,3- 14C 2]malonyl-CoA and from [1- 14C]acetyl-CoA plus partially purified rat liver acetyl-CoA carboxylase. 2. 2. A wide range (C 4:0–C 18:0) of fatty acids was synthesised and the proportions were modified by substrate concentrations in the same manner as for purified rabbit mammary gland fatty acid synthetase. 3. 3. The relative amount of radioactivity incorporated from added acetyl-CoA and malonyl-CoA depended on the substrate concentrations used. At excess acetyl-CoA to malonyl-CoA, greater amounts of acetyl-CoA were incorporated than theoretically expected from the malonyl-CoA pathway. At excess malonyl-CoA, less acetyl-CoA was incorporated than theoretically expected. 4. 4. An increase in the chain-length of fatty acids synthesised from malonyl-CoA was observed with increasing malonyl-CoA concentrations and malonyl-CoA to acetyl-CoA ratios. A similar increase was observed when increasing amounts of a malonyl-CoA generating system were added. However, at the same overall rate of synthesis, a lower proportion of long-chain fatty acids was synthesised from carboxylated acetyl-CoA than from added malonyl-CoA. 5. 5. It is suggested that acetyl-CoA carboxylase may carboxylate acetate bound to fatty acid synthetase.