title: Relationship between structure and substrate-chain-length specificity of mitochondrial very-long-chain acyl-coenzyme A dehydrogenase.
abstract: Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) is one of four enzymes which catalyze the initial step of the mitochondrial beta-oxidation with different but overlapping substrate-chain-length specificities. A450P, a variant of VLCAD identified in a patient with VLCAD deficiency, showed abnormal substrate-chain-length specificity. Based on this mutation, we studied the relationship between the structure and substrate-chain-length specificity of VLCAD. When VLCAD was treated with trypsin, a homodimer protein of a 48-kDa polypeptide deprived of both the amino-terminal 22 amino acids and the carboxyl-terminal 145 amino acids of VLCAD was obtained. Six Ala450 variants and tryptic-VLCAD exhibited similar substrate specificities. Effects of long-chain acyl-CoA on the tryptic cleavage and changes in the catalytic properties by deprivation of the carboxyl-terminal region suggest that this region interacts with the fatty acyl moiety of long-chain acyl-CoA. Thus, both Ala450 and the carboxyl-terminal region, which are not shared by other acyl-CoA dehydrogenases, are likely to be the determinating factors in the substrate-chain-length specificity of VLCAD.
authors.affiliation: Department of Biochemistry, Shinshu University School of Medicine, Matsumoto, Nagano, Japan. msouri@med.id.yamagata-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Souri
authors.forename: T
authors.initials: T
authors.lastname: Aoyama
authors.forename: S
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000409:Alanine / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology*; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D000214:Acyl Coenzyme A; D017931:DNA Primers; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D000409:Alanine