Fatty acid beta oxidation is the source of malonyl‐CoA for fatty acid chain elongation in rat heart

Abstract

In rat hearts perfused with [16,16,16‐d3]palmitic acid (M+3), some of the perfused palmitate underwent chain elongation to form M+3 stearoylcarnitine. No M+5 stearoylcarnitine was found indicating that unlabeled malonyl‐CoA served as the chain extender. Based on our data that peroxisomal fatty acid oxidation is the source of carbon units for malonyl‐CoA, in follow‐up experiments we asked whether fatty acid β‐oxidation of palmitate accounted for the chain elongation. Rat hearts were perfused in the working mode with [1,2,3,4‐13C4]palmitic acid (M+4) and the isotopic patterns analyzed using LC/MS/MS and a newly available algorithm. The presence of myristoylcarnitine with M+2 provides evidence for β‐oxidation of perfused M+4 palmitic acid. The relative amount of this mass isotopomer accounts for 82.5%. On the other hand, the 72% relative amount of M+4 species in stearoylcarnitine (corrected by the 21% relative amount of unlabeled, M+0 species) clearly shows that a significant fraction of the perfused palmitate was chain elongated. In addition to M+4 species, there also was a significant amount of M+6 stearoylcarnitine (22% corrected by the M+0 species). The formation of M+6 stearoylcarnitine can be explained only by β‐oxidation of the perfused palmitate and conversion of the M+2 acetyl‐CoA to M+2 malonyl‐CoA which serves as the acceptor for M+4 palmitoyl‐CoA.Supported by: DK‐066107 and POI AG15885.