title: Double bond removal from odd-numbered carbons during peroxisomal beta-oxidation of arachidonic acid requires both 2,4-dienoyl-CoA reductase and delta 3,5,delta 2,4-dienoyl-CoA isomerase.
abstract: The pathway for the peroxisomal beta-oxidation of arachidonic acid (5,8,11,14-20:4) was elucidated by comparing its metabolism with 4,7,10-hexadecatrienoic acid (4,7,10-16:3) and 5,8-tetradecadienoic acid (5,8-14:2) which are formed, respectively, after two and three cycles of arachidonic acid degradation. When [1-14C]4,7,10-16:3 was incubated with peroxisomes in the presence of NAD+ and NADPH, it resulted in a time-dependent increase in the production of acid-soluble radioactivity which was accompanied by the synthesis of 2-trans-4,7,10-hexadecatetraenoic acid and two 3,5,7,10-hexadecatetraenoic acid isomers. The formation of conjugated trienoic acids suggests that peroxisomes contain delta 3,5,delta 2,4-dienoyl-CoA isomerase with the ability to convert 2-trans-4,7,10-hexadecatetraenoic acid to 3,5,7,10-hexadecatetraenoic acid. When 1-14C-labeled 6,9,12-octadecatrienoic acid or 7,10,13,16-docosatetraenoic acid was incubated without nucleotides, the 3-hydroxy metabolites accumulated, since further degradation requires NAD(+)-dependent 3-hydroxyacyl-CoA dehydrogenase. When [1-14C]5,8,11,14-20:4 was incubated under identical conditions, no polar metabolite was detected, but 2-trans-4,8,11,14-eicosapentaenoic acid accumulated. When NADPH was added to incubations, 3-hydroxy-8,11,14-eicosatrienoic, 2-trans-4,8,11,14-eicosapentaenoic, 2-trans-8,11,14-eicosatetraenoic, and 8,11,14-eicosatrienoic acids were produced. Analogous compounds were formed from [1-14C]5,8-14:2. Our results show that the removal of double bonds from odd-numbered carbons in arachidonic acid thus requires both NADPH-dependent 2,4-dienoyl-CoA reductase and delta 3,5,delta 2,4-dienoyl-CoA isomerase. One complete cycle of 5,8-14:2 and 5,8,11,14-20:4 beta-oxidation yields, respectively, 6-dodecenoic and 6,9,12-octadecatrienoic acids.
authors.affiliation: Department of Medical Biochemistry, Ohio State University, Columbus 43210, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Luthria
authors.forename: S P
authors.initials: SP
authors.lastname: Baykousheva
authors.forename: H
authors.initials: H
authors.lastname: Sprecher
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D019748:Carbon-Carbon Double Bond Isomerases; D044943:Fatty Acid Desaturases / Q000502:physiology*; D007535:Isomerases / Q000502:physiology*; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D044925:Oxidoreductases Acting on CH-CH Group Donors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016718:Arachidonic Acid; D009249:NADP; D044943:Fatty Acid Desaturases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C100153:2,4-dienoyl-CoA reductase; D007535:Isomerases; D019748:Carbon-Carbon Double Bond Isomerases; C085575:delta(3,5),delta(2,4)-dienoyl-CoA isomerase