Fatty acid synthesis in adipose tissue. II. Enzymatic synthesis of branched chain and odd-numbered fatty acids.

Recent studies have done much to clarify the biosynthetic mechanism of normal long chain fatty acid synthesis (l-$)., However, very little is known about the biogenesis of odd-m bered and branched long chain fatty acids. Odd-numbered fat@ acids have been identified as minor components of ruminant milk (5), human milk (6), human blood (7), human sebum (8), rat phospolipids (9), and the lipids of the mold Xporidesmium bakeri (10). The branched long chain fatty acids (iso and anteiso acids) have been found in small amounts in butter fat (11)) ewe milk fat (12), woolwax (13)) and human sebum (8), human milk (6), and human blood (7). Using the isolated perfused cow’s udder, James et al. (14) have found that odd-numbered fatty acids are formed by the condensation of propionate with acetate. Feller and Feist (15) have reported that slices from adipose tissue incorporate propionic acid-l-Cl4 into long chain fatty acids as efficiently as acetate. On the other hand, Gerson (16) concluded from experiments with intravenously injected valeric acid-l-CY4 that valeric acid was not the direct precursor of the odd-numbered fatty acids present in the butter fat of the cow. In 1952, ElShazly (17) demonstrated that micro-organisms in the rumen of sheep could deaminate amino acids to form C-4 and C-5 branched chain acids (isobutyric,isovaleric, and oc-methylbutyric acids), and he suggested that these acids might be the precursors of the long chain iso and anteiso acids found in the milk fat of ruminants. In experiments with the perfused cow’s udder, Verbeke et al. (18) found that isovaleric acid-l-Cl4 is not incorporated into iso acids more efficiently than the normal acids. James et al. reported that acetate-2-C14 incubated with human whole blood is incorporated into all of the odd-numbered straight and branched chain fatty acids (7), but Gerson et al. reported (16) that acetate was incorporated into the anteiso acids more slowly than into normal acids. In the previous paper (19), we have described a partially purified soluble enzyme system obtained from adipose tissue of the rat which synthesizes long chain fatty acids from acetyl coenzyme A and malonyl coenzyme A. This paper describes the biosynthesis of odd-numbered, iso and anteiso fatty acids from propionyl coenzyme A, isobutyryl coenzyme A, isocaproyl coenzyme A, isovaleryl coenzyme A, and cY-methylbutyryl coenzyme A by this enzyme system. A preliminary report of these findings has been presented (20).