Lysophospholipase, lysophospholipid

Two possible pathways for the biosynthesis of 2-AG have been proposed (1) a phospholipase C (PLC) hydrolysis of membrane phospholipids followed by a second hydrolysis of the resulting 1,2-diacylglycerol by diacylglycerol lipase or (2) a phospholipase Ai (PLA,) activity that generates a lysophospholipid, which in turn is hydrolyzed to 2-AG by lysophospholipase C (Fig. 5) (Piomelli, 1998). Alternative pathways may also exist from either triacylglycerols by a neutral lipase activity or lysophosphatidic acid by a dephosphorylase. The fact that PLC and diacylglycerol lipase inhibitors inhibit 2-AG formation in cortical neurons supports the contention that 2-AG is, at least predominantly, biosynthesized by the PLC pathway (Stella, 1997). However, a mixed pathway may also be plausible. 

Most cells continually degrade and replace their membrane lipids. For each hydrolyzable bond in a glycerophospholipid, there is a specific hydrolytic enzyme in the lysosome (Fig. 10-15). Phospholipases of the A type remove one of the two fatty acids, producing a lysophospholipid. (These esterases do not attack the ether link of plasmalogens.) Lysophospholipases remove the remaining fatty acid. 

Many of the phospholipases, on the other hand, are very selective enzymes. The pancreatic phospholipase 2 (or phospholipase A2) hydrolyzes only esters in position 2 of sn-3 phospholipids i.e., the enzyme is stereospecific (Table II). Phospholipases I (or Ai) attack only the I-position. Lysophospholipases remove the remaining fatty acid, either in position I or 2, from the lysophospholipid. Phospholipases play a role in the post-mortem degradation of meat and fish. 

Enzymes that hydrolyze lysophospholipids are found in nearly all tissues and organisms. They seem to be non-specific esterases of the serine-histidine type (25) and hardly deserve the name lysophospholipase because they also hydrolyze esters other than phospholipids. They should probably be considered together with such enzymes as cholesterol esterases and monoglyceride lipases as amphiphilic carboxyl ester hydrolases. These non-specific esterases have a preference for amphiphilic (hydrophilic-lipophilic) substrates. Such an enzyme may perhaps hydrolyze lysophospholipis, monoglycerides, diglycerides, and cholesterol esters. 

The phospholipases A, (PLAjS) comprise a large group of 1-acyl hydrolases, some of which also degrade neutral lipids (lipases) or remove the acyl group at position 2 in addition to that at position 1 (PLB), and thus must have lysophospholipase activity. Where the enzyme appears to show low selectivity for the sn-l or sn-2 position, the term phospholipase A is used. The term phospholipase B should be restricted to those enzymes where the mechanism involves minimal accumulation of lysophospholipid product. In this section, we consider various enzymes of the PLA type that do not fit a more precise definition in terms of acyl chain selectivity. 

The distinction between PLB and lysophospholipases is not clear [2] since both diacyl-and monoacyl-phospholipids are substrates. As discussed above (Section 2.1), a working definition of these enzymes can be based on the extent to which the lysophospholipid... 

Figure 2. Sites of action of various types of phospholipases on phosphatidylcholine. Lysophospholipase hydrolyzes the carboxyl ester bond of a lysophospholipid (i.e., lysophosphatidylcholine).

Figure 1.2 suggests a mechanism for arachidonic acid release in thrombin-stimulated human blood platelets. Phospholipase A2 acts selectively on 1-acyl-2-arachidonoyl-phospholipids, of which the most important quantitatively is phosphatidylcholine, to liberate arachidonic acid and produce lysophospholi-pids. These lysophospholipids are subsequently hydrolysed in part by lysophospholipase to produce mainly glycerophosphocholine and smaller... 

Ferguson, C. Prestwich, G. Madan, D. Fluorogenic assay for lysophospholipase D activity using fluorogenic lysophospholipid derivatives as substrates, and diagnostic and screening applications. U.S. Pat. Appl. Publ. US 20100260682, 2010. 

The function(s) of lysophospholipases is unclear. It has been suggested that in mammalian tissues they help to prevent the build-up of lytic lysophospholipids. 

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