Kitamura Takuya, Naganuma Tatsuro, Abe Kensuke, Nakahara Kanae, Ohno Yusuke, Kihara Akio
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Biochim Biophys Acta. 2013 Aug;1831(8):1395-401. doi: 10.1016/j.bbalip.2013.05.007. Epub 2013 May 27.
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.
活性醛的积累与多种疾病的发生有关。醛脱氢酶（ALDHs）通过将醛氧化为相应的羧酸来解毒醛。在19种人类ALDHs中，ALDH3A2是唯一已知的催化包括通过鞘脂代谢产生的C16醛（十六醛和反式-2-十六烯醛）在内的长链脂肪醛氧化的ALDH。在本研究中，我们已确定ALDH3B1在体外对C16醛也具有活性，并证明ALDH3B1的过表达可恢复ALDH3A2缺陷细胞中的鞘脂代谢。此外，我们已确定ALDH3B1通过其C末端双脂化（棕榈酰化和异戊二烯化）定位于质膜，并表明异戊二烯化对于对十六醛的活性尤为重要。由于敲低ALDH3B1不会导致ALDH3A2缺陷细胞中鞘脂代谢的进一步受损，因此ALDH3B1可能的生理功能是氧化质膜中产生的脂质衍生醛，而不参与内质网中的鞘脂代谢。
