Deficiency of phosphatidylethanolamine synthesis: consequences for skeletal muscle.

hosphatidylethanolamine (PE) is a major gl ycer ophospholipid PL) in cellular and organellar membranes, and dysregulation of E synthesis has been associated with ener gy o v er-stora ge and nsulin resistance. 1 Due to the small size of its ethanolamine eadgr oup r elati v e to the v olume occupied by its long and, in articular, unsaturated fatty acyl side chains (which impart a kink” to the molecule), PE forms a conical shape. 2 This moleclar structure is key to sculpting the curv atur e of the inner layer f cellular and organellar membranes, where PE is quantitati v el y he most abundant type of PL. 3 In organelles where a high degree of membrane curv atur e s critical for the translation of structure to function, such s in the cristae that form the inner mitochondrial memranes, increases in PE content can impr ov e performance, hile losses can result in dysfunction that is so critical as o be incompatible with cellular and organismal life. 4 While his provides a direct connection between PE and the conrol of energy metabolism, recent studies demonstrate addiional roles for this gl ycer olipid in the regulation of wholeody metabolic homeostasis that are both complex and overlaping. For example, PE is primarily synthesized in the Kennedy athw ay thr ough the cytidine diphosphate (CDP)-ethanolamine athw ay, wher e CTP:phosphoethanolamine c ytid ylyltr ansfer ase Pcyt2) catalyzes the second and rate-limiting step. Because iacylgl ycer ol (DAG) is a substrate in the third and final step f the PE-K ennedy pathw ay, limitations in Pcyt2 activity are ssociated with reduced utilization, and therefore increased t