Eicosanoids are potent lipid mediators involved in central physiological processes such as hemostasis, renal function and parturition. When formed in excess, eicosanoids become critical players in a range of pathological conditions, in particular pain, fever, arthritis, asthma, cardiovascular disease and cancer. Eicosanoids are generated via oxidative metabolism of arachidonic acid along the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. Specific lipid species are formed downstream of COX and LOX by specialized synthases, some of which reside on the nuclear and endoplasmic reticulum, including mPGES-1, FLAP, LTC4 synthase, and MGST2. These integral membrane proteins are members of the family “membrane-associated proteins in eicosanoid and glutathione metabolism” (MAPEG). Here we focus on this enzyme family, which encompasses six human members typically catalyzing glutathione dependent transformations of lipophilic substrates. Enzymes of this family have evolved to combat the topographical challenge and unfavorable energetics of bringing together two chemically different substrates, from cytosol and lipid bilayer, for catalysis within a membrane environment. Thus, structural understanding of these enzymes are of utmost importance to unravel their molecular mechanisms, mode of substrate entry and product release, in order to facilitate novel drug design against severe human diseases.

类花生酸是有效的脂质介体，参与诸如止血，肾功能和分娩等中枢生理过程。当过量形成时，类花生酸成为一系列病理状况的关键因素，特别是疼痛，发烧，关节炎，哮喘，心血管疾病和癌症。类花生酸通过花生四烯酸沿环氧合酶（COX）和脂氧合酶（LOX）途径的氧化代谢。特定的脂质种类是由专门的合成酶在COX和LOX的下游形成的，其中一些位于核和内质网上，包括mPGES-1，FLAP，LTC4合酶和MGST2。这些完整的膜蛋白是“类花生酸和谷胱甘肽代谢中的膜相关蛋白”（MAPEG）家族的成员。在这里，我们集中于这个酶家族，它包括六个通常催化亲脂性底物的谷胱甘肽依赖性转化的人类成员。该家族的酶已经进化为应对地形挑战和不利的能量学，后者将来自细胞溶胶和脂质双层的两种化学上不同的底物聚集在一起，以在膜环境中进行催化。从而，