Molecular Identification and Characterization of Two Medium-chain Acyl-CoA Synthetases, MACS1 and the Sa Gene Product

Abstract

In this study, we identified and characterized two murine cDNAs encoding medium-chain acyl-CoA synthetase (MACS). One, designated MACS1, is a novel protein and the other the product of the Sa gene (Sa protein), which is preferentially expressed in spontaneously hypertensive rats. Based on the murine MACS1 sequence, we also identified the location and organization of the human MACS1 gene, showing that the human MACS1 and Sa genes are located in the opposite transcriptional direction within a 150-kilobase region on chromosome 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 preferred fatty acid among C2-C6 fatty acids for Sa protein. Like Sa gene transcript, MACS1 mRNA was detected mainly in the liver and kidney. Subcellular fractionation revealed that both MACS1 and Sa protein are localized in the mitochondrial matrix. 14 C-Fatty acid incorporation studies indicated that acyl-CoAs produced by MACS1 and Sa protein are utilized mainly for oxidation.

The Streptomyces coelicolor Lipoate-protein Ligase Is a Circularly Permuted Version of the Escherichia coli Enzyme Composed of Discrete Interacting Domains

“…synthesis has been ascribed to a mitochondrial medium-chain acyl-CoA synthetase known as ACSM1 (34,35). This is an enzyme of broad acyl chain specificity, including several xenobiotics that contains each of the motifs of this well studied enzyme family (39,40). However, ACSM1 has been reported to convert both the natural (R)-and unnatural (S)-lipoate isomers to their adenylates and also uses GTP to produce lipoylguanylate, which is released from the enzyme to serve as a lipoyl transferase substrate (14).…”

High-fat diet, muscular lipotoxicity and insulin resistance

“…However, this premise is not true for medium-chain fatty acids; these fatty acids can be activated inside the mitochondrial matrix and do not rely on carnitine palmitoyltransferase 1 for mitochondrial uptake (Tol, 1975;Rasmussen et al 2002). Thus, even when neutral mediumchain fatty acids reach the mitochondrial matrix they can be activated to fatty acyl-CoA and directed to b-oxidation (Fujino et al 2001). Obviously, these fatty acids do not need to (and should not) be exported from the matrix, eliminating a role for UCP3 in the handling of these specific medium-chain fatty acids.…”

Familial juvenile hyperuricaemic nephropathy (FJHN): linkage analysis in 15 families, physical and transcriptional characterisation of the FJHN critical region on chromosome 16p11.2 and the analysis of seven candidate genes

“…Both rat and mouse homologues showed kidney and liver specific gene expression. 41 Three sequence variants, silent transitions c45T-C and c720G-A and c314insT were detected in Ks-2 gene. All of these variants were homozygous in both patients and controls.…”

“…A recent study identified the protein as a medium-chain acyl-CoA synthetase. 41 Six sequence variants were detected in the Ks-1 gene. Two transitions, c340G-A and c428T-C, changing 114Gln-Lys and 143Leu-Ser, respectively, transversion g1166C-A, and a homozygous single base pair deletion g3385delT were found in both patients and controls.…”