Integral Membrane Enzymes in Eicosanoid Metabolism: Structures, Mechanisms and Inhibitor Design

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