Molecular identification and characterization of two medium-chain Acyl-CoAsynthetases, MACS1 and the Sa gene product

In this study, we identified and characterized two murine cDNAs encoding me dium-chain acyl-CoA synthetase (MACS). One, designated MACS1, is a novel pr otein and the other the product of the Sa gene (Sa protein), which is prefe rentially expressed in spontaneously hypertensive rats. Based on the murine MACS1 sequence, we also identified the location and organization of the hu man MACS1 gene, showing that the human MACS1 and Sa genes are located in th e opposite transcriptional direction within a 150-kilobase region on chromo some 16p13.1. Murine MACS1 and Sa protein were overexpressed in COS cells, purified to homogeneity, and characterized. Among C4-C16 fatty acids, MACS1 preferentially utilizes octanoate, whereas isobutyrate is the most preferr ed fatty acid among C2-C6 fatty acids for Sa protein. Like Sa gene transcri pt, MACS1 mRNA was detected mainly in the liver and kidney. Subcellular fra ctionation revealed that both MACS1 and Sa protein are localized in the mit ochondrial matrix. C-14-Fatty acid incorporation studies indicated that acy l-CoAs produced by MACS1 and Sa protein are utilized mainly for oxidation.