Identification of genes mediating branched chain fatty acid elongation.

Saturated branched chain fatty acids (BCFA) terminating with either a prop-2-yl (iso) or sec-butan-2-yl (anteiso) group are common bioactive food components consumed from beef, fish, and dairy products. Little is known about the endogenous metabolism of BCFA and the enzymes mediating their interconversions. By using transient transfection studies, we report for the first time the substrate specificity of the elongase of very long chain fatty acids (ELOVL)1-7 toward anteiso-15:0 and iso-18:0, and assessed competition between BCFA and normal saturated fatty acids (n-SFA). ELOVL6 mediates elongation of anteiso-15:0→anteiso-17:0, while ELOVL3 is active toward iso-18:0→iso-20:0. Competition studies reveal n-16:0 competes with anteiso-15:0 for ELOVL6, while n-18:0 competes with iso-18:0 for ELOVL3. These competitions for elongation may have implications in specialized tissues where both BCFA and n-SFA are present at comparable levels.

The elongation of very long-chain fatty acid 6 gene product catalyses elongation of n-13 : 0 and n-15 : 0 odd-chain SFA in human cells.

Normal odd-chain SFA (OCSFA), particularly tridecanoic acid (n-13 : 0), pentadecanoic acid (n-15 : 0) and heptadecanoic acid (n-17 : 0), are normal components of dairy products, beef and seafood. The ratio of n-15 : 0:n-17 : 0 in ruminant foods (dairy products and beef) is 2:1, while in seafood and human tissues it is 1:2, and their appearance in plasma is often used as a marker for ruminant fat intake. Human elongases encoded by elongation of very long-chain fatty acid (ELOVL)1, ELOVL3, ELOVL6 and ELOVL7 catalyse biosynthesis of the dominant even-chain SFA; however, there are no reports of elongase function on OCSFA. ELOVL transfected MCF7 cells were treated with n-13 : 0, n-15 : 0 or n-17 : 0 (80 µm) and products analysed. ELOVL6 catalysed elongation of n-13 : 0→n-15 : 0 and n-15 : 0→n-17 : 0; and ELOVL7 had modest activity toward n-15 : 0 (n-15 : 0→n-17 : 0). No elongation activity was detected for n-17 : 0→n-19 : 0. Our data expand ELOVL specificity to OCSFA, providing the first molecular evidence demonstrating ELOVL6 as the major elongase acting on OCSFA n-13 : 0 and n-15 : 0 fatty acids. Studies of food intake relying on OCSFA as a biomarker should consider endogenous human metabolism when relying on OCSFA ratios to indicate specific food intake.