Studies on the Mechanism of Fatty Acid Synthesis

Abstract

Previous evidence (I, 2) indicated that the synthesis of long chain fatty acids from acetyl coenzyme A was catalyzed by two separate and distinct protein fractions derived from avian or mammalian livers.In addition to the enzyme fractions and ace&l coenzyme A there was an absolute requirement for adenosine triphosphate, Mn++, HC03-, and reduced triphosphopyridine nucleotide (2).The fatty acids synthesized were shown to be mainly palmitic acid which derived all of its carbon atoms from acetyl coenzyme A by a "head to tail" condensation of this metabolite (3).The requirement for bicarbonate was absolute, yet radiolabeled HCOs-was not incorporated into the palmitic acid.This observation led Gibson et al. ( 4) to postulate a catalytic role for HCOs-in the over-all reaction.A similar requirement for bicarbonate was reported by Klein ( 5) in studies on the synthesis of fatty acids by particulate preparations from yeast cells and by Squires and Stumpf (6) in their studies on fatty acid synthesis in extracts of avocado fruits.Recently, Wakil (7) isolated the first intermediate in the synthesis of long chain fatty acids from acetyl-CoA and thus split the reaction sequence into two parts.The first reaction was the formation of malonyl-CoA by the carboxylation of acetyl-CoA in the presence of ATP, Mn +f, and a biotin-containing enzyme, acetyl-CoA carboxylase (RI& according to the following equation: