Fatty Acid Metabolism

Abstract

The realization that carbohydrates can be converted to fat prompted several theories on the formation of fatty acids. For example, Emil Fischer proposed the “hexose condensation theory” where three sugar molecules condense to form a C₁₈ fatty acid after the hydroxyl groups have been reduced (Fischer, 1890). Later, it was proposed that acetaldehyde might serve as the initial substrate for fatty acid synthesis (Nencki, 1878). This was supported by the fact that the addition of acetaldehyde to the growth medium stimulates fatty acid production in several fungi (Haehn, 1921; Terroine and Bonnet, 1927; Ottke et al., 1951). Acetate was shown to be the C₂ precursor of fatty acids when radiolabeled acetic acid resulted in greater amounts of labeled fatty acids than carbohydrates (Sonderhoff and Thomas, 1937). Probably the two most important contributions to the elucidation of the fatty acid synthesis pathway was the discovery that acetyl-CoA is the “active” form of the C₂ substrate (Lynen and Reichert, 1951; Lynen et al., 1951), and that malonyl-CoA contributes all the carbons but two to the fatty acid molecule (Wakil, 1958; Wakil and Ganguly, 1959).