title: Brain microsomal fatty acid elongation is increased in abcd1-deficient mouse during active myelination phase.
abstract: The dysfunction of ABCD1, a peroxisomal ABC protein, leads to the perturbation of very long chain fatty acid (VLCFA) metabolism and is the cause of X-linked adrenoleukodystrophy. Abcd1-deficient mice exhibit an accumulation of saturated VLCFAs, such as C26:0, in all tissues, especially the brain. The present study sought to measure microsomal fatty acid elongation activity in the brain of wild-type (WT) and abcd1-deficient mice during the course of development. The fatty acid elongation activity in the microsomal fraction was measured by the incorporation of [2-(14)C]malonyl-CoA into fatty acids in the presence of C16:0-CoA or C20:0-CoA. Cytosolic fatty acid synthesis activity was completely inhibited by the addition of N-ethylmaleimide (NEM). The microsomal fatty acid elongation activity in the brain was significantly high at 3 weeks after birth and decreased substantially at 3 months after birth. Furthermore, we detected two different types of microsomal fatty acid elongation activity by using C16:0-CoA or C20:0-CoA as the substrate and found the activity toward C20:0-CoA in abcd1-deficient mice was higher than the WT 3-week-old animals. These results suggest that during the active myelination phase the microsomal fatty acid elongation activity is stimulated in abcd1-deficient mice, which in turn perturbs the lipid composition in myelin.
authors.affiliation: Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan. masa@pha.u-toyama.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Kawamichi
authors.affiliation: Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shimura
authors.affiliation: Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Imanaka
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000172:deficiency*; D000326:Adrenoleukodystrophy; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D008316:Malonyl Coenzyme A / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008861:Microsomes / Q000378:metabolism*; D009186:Myelin Sheath / Q000235:genetics*
chemical_list: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; C552836:Abcd1 protein, mouse; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D008316:Malonyl Coenzyme A; D007770:L-Lactate Dehydrogenase; D005033:Ethylmaleimide
keywords: ABCD1; Microsomal fatty acid elongation; Very long chain fatty acid; X-linked adrenoleukodystrophy