title: Bimodal occurrence of aspartoacylase in myelin and cytosol of brain.
abstract: The growing use of N-acetylaspartate as an indicator of neuronal viability has fostered interest in the biological function(s) of this unusual amino acid derivative. In considering the various physiological roles that have been proposed for this relatively abundant molecule one is obliged to take into account its unusual metabolic compartmentalization, according to which synthesis and storage occur in the neuron and hydrolytic cleavage in the oligodendrocyte. The latter reaction, catalyzed by aspartoacylase (ASPA), produces acetyl groups plus aspartate and has been proposed to occur in both soluble and membranous subfractions of white matter. Our study supports such bimodal occurrence and we now present immunoblot, proteomic, and biochemical evidence that the membrane-bound form of ASPA is intrinsic to purified myelin membranes. This was supported by a novel TLC-based method for the assay of ASPA. That observation, together with previous demonstrations of numerous lipid-synthesizing enzymes in myelin, suggests utilization of acetyl groups liberated by myelin-localized ASPA for lipid synthesis within the myelin sheath. Such synthesis might be selective and could explain the deficit of myelin lipids in animals lacking ASPA.
authors.affiliation: Department of Neurology and Neurosciences, New Jersey Medical School, UMDNJ, Newark, New Jersey 07103, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Reuben
authors.initials: R
authors.lastname: Matalon
authors.forename: Gita
authors.initials: G
authors.lastname: Bhatia
authors.forename: Gusheng
authors.initials: G
authors.lastname: Wu
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Zi-Hua
authors.initials: ZH
authors.lastname: Lu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Ledeen
mesh_terms: D000581:Amidohydrolases / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000096:biosynthesis; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D001923:Brain Chemistry / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology*; D002855:Chromatography, Thin Layer; D003600:Cytosol / Q000201:enzymology*; D015151:Immunoblotting; D008563:Membrane Lipids / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000201:enzymology*; D009474:Neurons / Q000201:enzymology; D009836:Oligodendroglia / Q000201:enzymology; D040901:Proteomics
chemical_list: D008563:Membrane Lipids; D001224:Aspartic Acid; C000179:N-acetylaspartate; D000581:Amidohydrolases; C019751:aspartoacylase