title: Acyl-CoA thioesterase 9 (ACOT9) in mouse may provide a novel link between fatty acid and amino acid metabolism in mitochondria.
abstract: Acyl-CoA thioesterase (ACOT) activities are found in prokaryotes and in several compartments of eukaryotes where they hydrolyze a wide range of acyl-CoA substrates and thereby regulate intracellular acyl-CoA/CoA/fatty acid levels. ACOT9 is a mitochondrial ACOT with homologous genes found from bacteria to humans and in this study we have carried out an in-depth kinetic characterization of ACOT9 to determine its possible physiological function. ACOT9 showed unusual kinetic properties with activity peaks for short-, medium-, and saturated long-chain acyl-CoAs with highest V max with propionyl-CoA and (iso) butyryl-CoA while K cat/K m was highest with saturated long-chain acyl-CoAs. Further characterization of the short-chain acyl-CoA activity revealed that ACOT9 also hydrolyzes a number of short-chain acyl-CoAs and short-chain methyl-branched CoA esters that suggest a role for ACOT9 in regulation also of amino acid metabolism. In spite of markedly different K ms, ACOT9 can hydrolyze both short- and long-chain acyl-CoAs simultaneously, indicating that ACOT9 may provide a novel regulatory link between fatty acid and amino acid metabolism in mitochondria. Based on similar acyl-CoA chain-length specificities of recombinant ACOT9 and ACOT activity in mouse brown adipose tissue and kidney mitochondria, we conclude that ACOT9 is the major mitochondrial ACOT hydrolyzing saturated C2-C20-CoA in these tissues. Finally, ACOT9 activity is strongly regulated by NADH and CoA, suggesting that mitochondrial metabolic state regulates the function of ACOT9.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, C1-74, Karolinska University Hospital, SE-141 86, Stockholm, Sweden.
authors.forename: Veronika
authors.initials: V
authors.lastname: Tillander
authors.forename: Elisabet
authors.initials: E
authors.lastname: Arvidsson Nordström
authors.forename: Jenny
authors.initials: J
authors.lastname: Reilly
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Strozyk
authors.forename: Paul P
authors.initials: PP
authors.lastname: Van Veldhoven
authors.forename: Mary C
authors.initials: MC
authors.lastname: Hunt
authors.forename: Stefan E H
authors.initials: SE
authors.lastname: Alexson
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D016000:Cluster Analysis; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D013053:Spectrophotometry; D013869:Thiolester Hydrolases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D017931:DNA Primers; D005227:Fatty Acids; D024101:Mitochondrial Proteins; C587635:Acot10 protein, mouse; C587636:Acot9 protein, mouse; D013869:Thiolester Hydrolases