American Journal of Clinical Nutrition, Vol 8, 630-644, Copyright © 1960 by The American Society for Clinical Nutrition, Inc.

The Mechanism of Fatty Acid Synthesis

¹ From the Department of Biochemistry and Center for the Study of Aging, Duke University Medical Center, Durham, North Carolina

Evidence has been presented to show that there are two distinct systems for the synthesis of fatty acids. (1) The mitochondrial system is located in the mitochondria and involves the enzymes of the -oxidation system (thiolase, enoyl hydrase, -hydroxyacyl dehydrogenase) working in reverse plus the TPN-,--unsaturated fatty acyl CoA reductase enzyme. Both TPNH and DPNH are required for the synthesis. Essentially this system is for the elongation of the existing fatty acids by the addition of two-carbon units at a time. It is possible that this system may be responsible for the formation of stearate from palmitate, arachidonate from linoleate, etc.

(2) The non-mitochondrial system is located in the cytoplasm of the cell and catalyzes the conversion of AcCoA to palmitate in the presence of ATP, Mn⁺⁺, HCO₃^– and TPNH (DPNH may be substituted for TPNH at a slower rate). Acetyl CoA is condensed with HCO₃^– to form malonyl CoA, a reaction which is catalyzed by acetyl CoA carboxylase (a biotin-containing enzyme) in the presence of ATP and Mn⁺⁺. The biotin is bound to the protein and evidence has verified that it does participate in the formation of malonyl CoA. Malonyl CoA condenses with acetyl CoA to form several intermediates which can be reduced by TPNH to form the saturated fatty acids.

This system appears to be the main pathway for fatty acid synthesis, and it is widely distributed in living organisms. So far this system has been isolated from pigeon liver, chicken liver, rat liver, rat kidney, yeast cells and avocados.

The enzymic system for the synthesis of short-chain fatty acids in the mammary gland may be different from the aforementioned systems, but more information is needed before final judgment can be made.