title: Substrate specificity, plasma membrane localization, and lipid modification of the aldehyde dehydrogenase ALDH3B1.
abstract: The accumulation of reactive aldehydes is implicated in the development of several disorders. Aldehyde dehydrogenases (ALDHs) detoxify aldehydes by oxidizing them to the corresponding carboxylic acids. Among the 19 human ALDHs, ALDH3A2 is the only known ALDH that catalyzes the oxidation of long-chain fatty aldehydes including C16 aldehydes (hexadecanal and trans-2-hexadecenal) generated through sphingolipid metabolism. In the present study, we have identified that ALDH3B1 is also active in vitro toward C16 aldehydes and demonstrated that overexpression of ALDH3B1 restores the sphingolipid metabolism in the ALDH3A2-deficient cells. In addition, we have determined that ALDH3B1 is localized in the plasma membrane through its C-terminal dual lipidation (palmitoylation and prenylation) and shown that the prenylation is required particularly for the activity toward hexadecanal. Since knockdown of ALDH3B1 does not cause further impairment of the sphingolipid metabolism in the ALDH3A2-deficient cells, the likely physiological function of ALDH3B1 is to oxidize lipid-derived aldehydes generated in the plasma membrane and not to be involved in the sphingolipid metabolism in the endoplasmic reticulum.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitamura
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Naganuma
authors.forename: Kensuke
authors.initials: K
authors.lastname: Abe
authors.forename: Kanae
authors.initials: K
authors.lastname: Nakahara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohno
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology* / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D054878:Lipoylation / Q000502:physiology*; D013107:Sphingolipids / Q000378:metabolism; D013379:Substrate Specificity / Q000502:physiology
chemical_list: D000447:Aldehydes; D013107:Sphingolipids; C051750:2-hexenal; D000445:Aldehyde Oxidoreductases; C520012:ALDH3B1 protein, human; C001647:hexadecanal