Eugene P. Kennedy and Albert L. Lehninger. The Ben May Laboratory for Cancer Research and Department of Biochemistry University of Chicago, Chicago

In the past few years, dramatic advances have been made in elucidating the pattern of enzymatic oxidation of fatty acids. As a result of the intensive and revealing application of the isotope tracer technique to many phases of fatty acid metabolism and the relatively recent successes in restoring the processes of fatty acid and acetoace-tate oxidation in properly supplemented cell-free systems, the general framework of fatty acid metabolism is now quite well defined. The discovery of the role of acetyl coenzyme A as the long-sought " C2 unit" so important in fatty acid metabolism has opened the way to further advances. The achievement of Stadtman and Barker (56) in demonstrating fatty acid oxidation and synthesis in completely soluble enzyme extracts of C. kluyveri and the very recent reports of comparable success in solubilizing the fatty acid oxidase system of animal tissues (14, 20) give considerable hope that the complex enzyme mixtures may be fractionated and single enzymatic transformations studied. It is only by such means that an understanding of fatty acid metabolism as detailed and as comprehensive as that of carbohydrate metabolism may be achieved.

This discussion will consider the mechanism of fatty acid oxidation under three main headings: (1) the properties of the fatty acid oxidase system of animal tissues; (2) the mechanism of acetoacetate formation; and (3) the significance of recent work on fatty acid oxidation and synthesis in extracts of C. kluyveri.