title: Characterization of mouse homolog of brain acyl-CoA hydrolase: molecular cloning and neuronal localization.
abstract: Acyl-CoA hydrolase could provide a mechanism via its potency to modulate cellular concentrations of acyl-CoAs for the regulation of various cellular events including fatty acid metabolism and gene expression. However, only limited evidence of this is available. To better understand the physiological role of this enzyme, we characterized a mouse brain acyl-CoA hydrolase, mBACH. The cloned cDNA for mBACH encoded a 338-amino-acid polypeptide with >95% identity to the human and rat homologs, indicating that the BACH gene is highly conserved among species. This was supported by the similarity in genomic organization of the BACH gene between humans and mice. Bacterially expressed mBACH was highly active against long-chain acyl-CoAs with a relatively broad specificity for chain length. While palmitoyl-CoA hydrolase activity was widely distributed in mouse tissues, it was marked in the brain, consistent with mBACH being almost exclusively distributed in this tissue, where >80% of the enzyme activity was explained by mBACH present in the cytosol. Immunohistochemistry demonstrated a neuronal localization of mBACH in both the central and peripheral nervous systems. In neurons, mBACH was distributed throughout the cell body and neurites. Although four isoforms except mBACH itself, that may be generated by the alternative use of exons of a single mBACH gene, were cloned, their mRNA levels in the brain were estimated to be negligible. However, a 50-kDa polypeptide besides the major one of 43-kDa seemed to be translated from the mBACH mRNA with differential in-frame ATG triplets used as the initiation codon. These findings will contribute to the functional analysis of the BACH gene using mice including genetic studies.
authors.affiliation: Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, 192-0392, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kuramochi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takagi-Sakuma
authors.forename: Mari
authors.initials: M
authors.lastname: Kitahara
authors.forename: Ryoko
authors.initials: R
authors.lastname: Emori
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Asaba
authors.forename: Reiko
authors.initials: R
authors.lastname: Sakaguchi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Junji
authors.initials: J
authors.lastname: Kuroda
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hiratsuka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nagae
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suga
authors.forename: Junji
authors.initials: J
authors.lastname: Yamada
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology*; D003001:Cloning, Molecular; D018387:Codon, Initiator / Q000235:genetics; D003600:Cytosol / Q000201:enzymology; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006066:Gonads / Q000201:enzymology; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D051379:Mice / Q000235:genetics*; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009206:Myocardium / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D016501:Neurites / Q000201:enzymology; D009447:Neuroblastoma / Q000473:pathology; D009928:Organ Specificity; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014407:Tumor Cells, Cultured; D014781:Viscera / Q000201:enzymology
chemical_list: D018387:Codon, Initiator; D018076:DNA, Complementary; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C521939:Acot7 protein, mouse; D010170:Palmitoyl-CoA Hydrolase