title: [2,4-Dienoyl-CoA reductases: from discovery toward pathophysiological significance].
abstract: 2,4-Dienoyl-CoA reductases from Escherichia coli and bovine liver were purified and characterized by the authors and almost simultaneously by Kunau and his colleagues around the early 1980s. The authors purified 2,4-dienoyl-CoA reductase from rat liver, cloned its cDNA and expressed its active form in Escherichia coli for the first time. Schulz and his colleagues have elaborately shown that mutant E. coli, in which the activity of the 2,4-dienoyl-CoA reductase is reduced to 12% of that in the parental strain, can grow on oleic acid but not on (Z)-6-octadecenoic acid as a sole carbon source. A single sporadic human fatality, in which the activities of 2,4-dienoyl-CoA reductases were reduced and accumulation of (2E,4Z) 2,4-decadienoylcarnitine was observed, has so far been reported. These taken together with the discovery of a novel delta3,5-delta2,4-dienoyl CoA isomerase and the absence of 3-hydroxyacyl-CoA epimerase have caused the classical metabolic pathway for beta-oxidation of unsaturated fatty acids, depicted by Stoffel in 1965, to be rewritten, and 2,4-dienoyl-CoA reductases are now known to be essential to beta-oxidation of unsaturated fatty acids. Very recently a single amino acid substitution adjacent to the NADPH binding site has been reported in pigs, suggesting that single nucleotide polymorphism will also be found to occur in humans.
authors.affiliation: Pharmacovigilance and Product Information Department, Takeda Chemical Industries, Ltd.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kimura
authors.forename: Michinao
authors.initials: M
authors.lastname: Mizugaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujino
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Morishima
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D019748:Carbon-Carbon Double Bond Isomerases; D002417:Cattle; D004926:Escherichia coli / Q000201:enzymology / Q000254:growth & development; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008930:Mitochondria, Liver / Q000201:enzymology; D009249:NADP; D019301:Oleic Acid; D010084:Oxidation-Reduction; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D051381:Rats
chemical_list: D005231:Fatty Acids, Unsaturated; D019301:Oleic Acid; D009249:NADP; D044925:Oxidoreductases Acting on CH-CH Group Donors; C100153:2,4-dienoyl-CoA reductase; D019748:Carbon-Carbon Double Bond Isomerases; C085575:delta(3,5),delta(2,4)-dienoyl-CoA isomerase