58] Lysophospholipase D

Abstract

Publisher Summary This chapter focuses on lysophospholipase D, which was discovered during studies of plasmalogen biosynthesis in rat brain. Lysophospholipase D acts on 1- O -alkyl-2-lyso- sn -glycero-3-phosphocholine (1- O -alkyl-GPC) and the plasmalogen species 1- O -alk-1ʹ-enyl-2-1yso-GPE and on 1- O -alkyl-GPE. Lysophospholipase D is also believed in a number of tissues of the rat including liver, testes, lung, intestine, and kidney. The substrate specificity of the rat liver lysophospholipase D indicates that the enzyme does not hydrolyze acyl-linked substrates such as 1-acyl-2-1yso-GPC. Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-GPC) is not hydrolyzed by lysophospholipase D unless the 2-acetyl group is removed by an acetylhydrolase. The physiological role of lysophospholipase D is unclear. One of the most remarkable characteristics of the enzyme is its apparent high selectivity for ether-linked species, and in particular the 1- O -alkyl species. No hydrolysis of 1-acyl-2-lyso-GPC is observed when it is codispersed in equimolar concentration with 1-alkyl-2-1yso-GPC, even though up to 50% of the alkyl-linked substrate is hydrolyzed. The high specificity for alkyl-linked species suggests a special role for the enzyme in the metabolism of these lipids. The enzyme may also play a role in the metabolism of PAF and could possibly provide a pathway for the production of 1-alkyl-2-acetyl- sn -glycero-3-phosphate via acetylation of the 1-alkyl-2-lyso- sn -glycero-3-phosphate, thus providing a substrate for the putative de novo pathway of PAF biosynthesis. Another possible role for lysophospholipase D could be to provide a mechanism for interconversion of choline- and ethanolamine-linked ether species.