THEM86B hydrolyses PMCHO, PMETAM

Plasmalogens (1-alk-1'-enyl- 2-acyl-sn-glycero-3-phosphoethanolamine or 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphocholine) are abundant (4-32% of total membrane phospholipids) membrane glycerophospholipids found throughout bacterial, invertebrate and vertebrate animal kingdoms. They differ from other membrane glycerophospholipids by having an alk-1'-enyl ether-linked chain at the glycerol sn-1 carbon. Plasmalogens are critical for normal cell function and development and their levels are altered in disease states; decreased in peroxisomal disorders, Alzheimer disease and Down syndrome, and elevated in tumours. Plasmalogens can be hydrolysed into lysoplasmalogens (1-alk-1'-enyl-2-hydroxy-sn-glycero-3-phosphoethanolamine or 1-alk-1'-enyl-2-hydroxy-sn-glycero-3-phosphocholine). Lysoplasmalogens are bioactive metabolites which have membrane-perturbing and cell lysis effects. Their levels are normally maintained at very low levels in cells, with lysoplasmalogens formed by plasmalogen hydrolysis converted back to plasmalogen in a transacylation reaction (a remodelling pathway). Alternatively, lysoplasmalogen may be degraded enzymatically by several hydrolytic enzymes that includes lysoplasmalogenase (THEM86B). THEM86B catalyses the hydrolysis of the vinyl ether bond of lysoplasmenylcholine (PMCHO) and lysoplasmenylethanolamine (PMETAM) to form a fatty aldehyde and glycerophosphocholine (GPCHO) and glycerophosphoethanolamine (GPETAM) respectively. THEM86B is localised to the ER membrane of liver and small intestinal mucosal cells where it is highly active and is probably an important enzyme there, maintaining the balance between plasmalogen and lysoplasmalogen, thereby preserving membrane stability and function (Wu et al. 2011, Honsho et al. 2015).

质膜磷脂酰甘油（1-烷-1'-烯基-2-酰基-sn-甘油-3-磷酸乙醇胺或1-烷-1'-烯基-2-酰基-sn-甘油-3-磷酸胆碱）称为质膜脂质，其含量丰富，占总膜磷脂的4%-32%，广泛分布于细菌、无脊椎动物和脊椎动物界。与其他膜磷脂酰甘油相比，其特征在于甘油sn-1碳上存在烷-1'-烯基醚连接的链。质膜脂质对于细胞的正常功能和发育至关重要，其水平在疾病状态下会发生改变；在过氧化物酶体疾病、阿尔茨海默病和唐氏综合症中降低，而在肿瘤中升高。质膜脂质可以被水解成溶血质膜脂质（1-烷-1'-烯基-2-羟基-sn-甘油-3-磷酸乙醇胺或1-烷-1'-烯基-2-羟基-sn-甘油-3-磷酸胆碱）。溶血质膜脂质是具有膜干扰和细胞溶解作用的生物活性代谢物，其在细胞中通常维持在极低水平，通过质膜脂质水解形成的溶血质膜脂质在转酰基反应（一种重塑途径）中重新转化为质膜脂质。或者，溶血质膜脂质可能被多种水解酶（包括溶血质膜脂质酶THEM86B）酶促降解。THEM86B催化溶血质膜鞘磷脂（PMCHO）和溶血质膜鞘乙醇胺（PMETAM）的乙烯醚键的水解，分别形成脂肪酸醛和甘油磷胆碱（GPCHO）以及甘油磷乙醇胺（GPETAM）。THEM86B定位于肝脏和细小肠黏膜细胞的内质网膜上，在此处活性极高，可能是该区域中一种重要的酶，通过维持质膜脂质与溶血质膜脂质之间的平衡，从而保持膜稳定性和功能（Wu等，2011年；Honsho等，2015年）。