#N2ping official website Pc

These non-HKD enzymes are discussed here as a means of comparison. Non-HKD enzymes exhibiting PLD activity have divergent structures and catalytic mechanisms. These enzymes are members of the PLD superfamily, and are proposed to follow a similar reaction mechanism. A large subset of enzymes with PLD activity share a conserved HxKxxxxDx 6GSxN motif (HKD),18 or a variation thereof, that is responsible for catalytic activity.

#N2ping official website Pc

The majority of these enzymes hydrolyze phosphodiester bonds within phospholipids such as PC (classified as EC 3.1.4.4 17), but there are other enzymes ascribed to having PLD activity that hydrolyze neutral lipids and even polynucleotide backbone. To date, more than 4000 PLD enzymes have been entered in NCBI GenBank. PLD activity, an enzyme catalyzed hydrolysis of a phosphodiester bond, was first described in plants, 13, 14, 15, 16 and subsequently many enzymes from a range of viral, prokaryotic and eukaryotic organisms have been described as possessing PLD activity. These enzymes include lysophosphatidic acid acyltransferase (LPAAT) which acylates LPA, DAG kinase which phosphorylates DAG at the sn-3 position, and phospholipase D (PLD) which hydrolyzes the headgroup of a phospholipid, generally phosphatidylcholine (PC), triggering the release of choline. 11, 12 Signal generated PA is formed by enzymes that modify existing lipids. Every glycerophospholipid generated in eukaryotic membranes transitions through PA, a pathway characterized by Eugene Kennedy and his colleagues more than half a century ago. PA can be generated de novo 9, 10, 11 by sequential enzyme-catalyzed acylations of glycerol-3-phosphate, or in response to cell signaling pathways ( Figure 1). Aberrant PA signaling has been identified in multiple cancers, 6 neurodegeneration, 7 and platelet aggregation, 8 which makes proteins that mediate cellular levels of PA attractive as potential therapeutic targets. PA has been implicated in signaling cascades involving cell growth, proliferation, and survival. Several signaling proteins, including Raf-1 3, 4 and mTOR, 5 directly bind PA to mediate translocation or activation, respectively.

As a lipid second messenger, PA activates signaling proteins and acts as a node within the membrane to which signaling proteins translocate. 2 PA is also a precursor to other lipid signaling molecules including diacylglycerol (DAG) and lysophosphatidic acid (LPA). Because of the small head group, PA facilitates changes in lipid bilayer curvature that are important for membrane fusion events, such as vesicular trafficking and endocytosis. 1 This lipophilic glycerophospholipid has a phosphate head group, and as such serves not only a structural capacity in lipid bilayers, but also participates as an intermediate in lipid metabolism and as a signaling molecule. Phosphatidic acid (PA) is a critical phospholipid constituent in eukaryotic cell membranes, that accounts for 1–4 % of the total lipid.