Dermonecrotic toxins cleave the phosphodiester linkage between the phosphate and headgroup of certain phospholipids (sphingolipid and lysolipid substrates), forming an alcohol (often choline) and a cyclic phosphate. This toxin acts on lysophosphatidylethanolamine (LPE) and ceramide phosphoethanolamine (CPE) with high activity. This toxin acts on sphingomyelin (SM) with very low activity and is not active on lysophosphatidylserine (LPS), lysophosphatidylcholine (LPC) and lysophosphatidylglycerol (LPG). It acts by transphosphatidylation, releasing exclusively cyclic phosphate as second products. It is not surprising that spider toxins have affinity for ethanolamine-containing sphingolipids since they are common in insect prey (By similarity). Induces dermonecrosis, hemolysis, increased vascular permeability, edema, inflammatory response, and platelet aggregation (By similarity). an N-(acyl)-sphingosylphosphocholine = an N-(acyl)-sphingosyl-1,3-cyclic phosphate + choline N-hexanoyl-sphing-4-enine-1-phosphocholine = choline + N-(hexanoyl)-sphing-4-enine-1,3-cyclic phosphate an N-(acyl)-sphingosylphosphoethanolamine = an N-(acyl)-sphingosyl-1,3-cyclic phosphate + ethanolamine N-dodecanoyl-heptadecasphing-4-enine-1-phosphoethanolamine = ethanolamine + N-dodecanoyl-heptadecasphing-4-enine-1,3-cyclic phosphate a 1-acyl-sn-glycero-3-phosphoethanolamine = a 1-acyl-sn-glycero-2,3-cyclic phosphate + ethanolamine 1-tetradecanoyl-sn-glycero-3-phosphoethanolamine = 1-tetradecanoyl-sn-glycero-2,3-cyclic phosphate + ethanolamine Binds 1 Mg(2+) ion per subunit. Expressed by the venom gland. Belongs to the arthropod phospholipase D family. Class II subfamily. Class IIb sub-subfamily. The most common activity assay for dermonecrotic toxins detects enzymatic activity by monitoring choline release from substrate. Liberation of choline from sphingomyelin (SM) or lysophosphatidylcholine (LPC) is commonly assumed to result from substrate hydrolysis, giving either ceramide-1-phosphate (C1P) or lysophosphatidic acid (LPA), respectively, as a second product. However, two studies from Lajoie and colleagues (2013 and 2015) report the observation of exclusive formation of cyclic phosphate products as second products, resulting from intramolecular transphosphatidylation. Cyclic phosphates have vastly different biological properties from their monoester counterparts, and they may be relevant to the pathology of brown spider envenomation.