Enzymes of Fatty Acid Metabolism

The mechanism of the biological oxidation and synthesis of fatty acids has largely been elucidated during the past few years through work in several laboratories (l-7). This work resulted in the complete confirmation of Knoop’s B oxidation theory and of the main conclusions derived from the early work of Dakin and Embden. Perhaps one of the most important aspects of the recent work is the demonstration that fatty acid synthesis occurs by a reversal of /3 oxidation. Fatty acid oxidation is accomplished through the sequence of Reactions 1 through 5. At the end of each sequence (Reaction 5), a 2-carbon fragment is split off from the carboxyl end of the fatty acid chain as acetyl CoA.’ This can enter the citric acid cycle for complete oxidation or condense with another molecule of acetyl CoA to form acetoacetyl CoA and, through deacylation of the latter in the liver, acetoacetate. The fatty acyl CoA shortened by 2 carbon atoms (the other product of Reaction 5) can undergo a new oxidation and cleavage sequence, etc., through Reactions 2 to 5. The reversal of these reactions, from acetyl CoA and hydro-