Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hydrolysis of the alkenyl bonds of plasmenylcholine and plasmenylethanolamine by plasmalogenase, followed by hydrolysis of the resultant lysophospholipid by lysophospholipase, has been postulated as the major pathway for the catabolism of these plasmalogens. However, the postulation was based solely on the presence of plasmalogenase activity towards plasmenylethanolamine and plasmenylcholine in the brain. In this study we have demonstrated the absence of plasmalogenase activity for plasmenylcholine in the guinea pig heart under a wide range of experimental conditions. Plasmenylcholine was hydrolysed by phospolipase A2 activities in cardiac microsomal, mitochondrial and cytosolic fractions. Phospholipase A2 activities in these fractions had an alkaline pH optimum and were enhanced by Ca2+. The enzymes also displayed high specificity for plasmenylcholine with linoleoyl or oleoyl at the C-2 position. Lysoplasmalogenase activity for lysoplasmenycholine was also detected and characterized in the microsomal and mitochondrial fractions. Since the cardiac plasmalogenase is only active towards plasmenylethanolamine but not plasmenylcholine, the catabolism of these two plasmalogens must be different from each other. We postulate that the major pathway for the catabolism of plasmenycholine involves the hydrolysis of the C-2 fatty acid by phospholipase A2, and hydrolysis of the vinyl ether group of the resultant lysoplasmenylcholine by lysoplasmalogenase.
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PMID:The catabolism of plasmenylcholine in the guinea pig heart. 375 61

The biosynthesis of choline plasmalogens was investigated in Madin-Darby canine kidney cells to determine the source of the vinyl ether linkage. 1-O-[3H] Alk-1'-enyl-2-lyso-sn-glycero-3-phosphoethanolamine was a better precursor than 1-O-[3H]alkyl-2-lyso-sn-glycero-3-phosphocholine for the synthesis of 1-O-[3H]alk-1'-enyl-2-acyl-sn-glycero-3-phosphocholine; this suggests that the vinyl ether linkage in choline phosphoglycerides originates from ethanolamine plasmalogens. The contribution of N-methylation and base exchange enzymes to choline plasmalogen biosynthesis was assessed using 1-O-[3H]alkenyl-2-lyso-sn-glycero-3-[32P]phosphoethanolamine. While 1-O-[3H]alkenyl-2-acyl-sn-glycero-3-phosphocholine was formed from this precursor, the 32P was lost indicating that N-methylation and base exchange enzymes do not contribute significantly to the synthesis of choline plasmalogens. The conversion of a phosphono analog of 1-O-[3H]alkyl-2-lyso-sn-glycero-3-phosphoethanolamine, which is resistant to phospholipase D hydrolysis, to 1-O-[3H]alkenyl-2-acyl-sn-glycero-2-phosphocholine was observed demonstrating that phospholipase D is not required for choline plasmalogen biosynthesis. A Mg(2+)-dependent lysophospholipase C activity was detected in microsomes that actively hydrolyzed ether-linked lysophosphoglycerides as well as the lysophosphono analog. To assess the role of lysophospholipase C in shuttling 1-O-alk-1'-enyl-sn-glycerol (alkenylglycerol) from ethanolamine plasmalogens to choline plasmalogens, cells prelabeled with 1-O-[3H]alkenyl-2-lyso-sn-glycero-3-phosphoethanolamine were treated with 12-O-tetradecanoylphorbol-13-acetate. This resulted in the rapid deacylation of 1-O-[3H]alkenyl-2-acyl-sn-glycero-3-phosphoethanolamine to 1-O-[3H]alkenyl-2-lyso-sn-glycero-3-phosphoethanolamine and the subsequent generation of 1-O-[3H]alkenylglycerol. A concomitant 2-3-fold increase in 1-O-[3H]alkenyl-2-acyl-sn-glycero-3-phosphocholine was observed. These studies suggest that the alkenyl linkage in choline phosphoglycerides may originate from 1-O-alkenyl-2-lyso-sn-glycero-3-phosphoethanolamine through an enzymatic pathway involving lysophospholipase C to generate alkenylglycerol that is subsequently converted to choline plasmalogens.
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PMID:Identification of a lysophospholipase C that may be responsible for the biosynthesis of choline plasmalogens by Madin-Darby canine kidney cells. 824 86