NOVEL BIOSYNTHESIS PATHWAYS OF FOOD BASED ODD-NUMBERED CARBON CHAIN AND BRANCHED CHAIN FATTY ACIDS
Normal odd-numbered carbon chain fatty acids (n-OCFA) and branched chain fatty acids (BCFA) are both important components of dairy, beef and seafood. n-OCFA pentadecanoic acid (n-15:0) and heptadecanoic acid (n-17:0) are biomarkers of dairy, seafood and dietary fiber intake, because the consumption of n-15:0 and n-17:0 from these foods is reflected in human tissue FA composition. Difference in the ratios of n-15:0 to n-17:0 between foods and human tissues suggests that endogenous FA interconversion alters their ratio. BCFA are rare in most internal tissues, but present in skin sebaceous glands (SG), meibomian glands, and vernix caseosa in high levels. Little is known about the endogenous metabolism of n-OCFA and BCFA once ingested. Thus, we explored the substrate specificity of the human fatty acid interconversion enzymes, elongases ELOVL1-7, and desaturases SCD and FADS 1-2 toward n-OCFA and BCFA. The first study investigated the elongation of n-OCFA n-15:0 and n-17:0. ELOVLx transient transfected MCF-7 cells were treated with n-13:0, n-15:0 and n-17:0. ELOVL6 is the most active enzyme catalyzing n-13:0 → n-15:0 → n-17:0; ELOVL7 has modest activity toward n-15:0 (n-15:0 → n-17:0); no elongation activity was detected for any ELOVL toward n-17:0 → n-19:0. The second study focused on elongations of representative BCFA anteiso-15:0 and iso-18:0. ELOVL6 mediates anteiso-15:0 → anteiso-17:0, while ELOVL3 is active toward iso-18:0 → iso-20:0. Substrate competition studies between BCFA and n-FA for ELOVLx mediated elongations revealed n-16:0 is preferred over anteiso-15:0 for ELOVL6, while n-18:0 is preferred over iso-18:0 in ELOVL3 transfected cells. The third study characterized the FADS2 mediated Δ6-desaturation in stable FADS2 MCF-7 cells towards BCFA iso-16:0 → iso-6Z-16:1, iso-18:0 → iso-6Z-18:1, iso-17:0 → iso-6Z-17:1 and anteiso-17:0 → anteiso-6Z-17:1, and towards n-OCFA n-17:0 → n-6Z-17:1. FADS2, which is highly expressed in human SG, is responsible for desaturating BCFA and n-OCFA found on the skin. These novel pathways of n-OCFA and BCFA have implications in understanding their metabolism and inform the association between metabolic disease and gene-regulated FA composition shift.