Cytosolic lysophospholipase in cardiac myocytes and its inhibition by L-palmitoyl carnitine.
Since lysophosphatides have been implicated as arrhythmogenic metabolites, modulation of their catabolism in cardiac myocytes has been characterized. Rat cardiac myocytes and mesenchymal cells grown in culture were found to contain cytosolic lysophospholipase with specific activities of 1.3 +/- 0.1 and 0.9 +/- 0.1 nmol X mg-1 X min-1, respectively. Rat myocytic lysophospholipase had a molecular mass of approximately 20,000 daltons, estimated by gel filtration chromatography. Kinetic analysis of cytosolic myocytic lysophospholipase demonstrated a Michaelis constant of 11 microM, a pH optimum of 8.0, and competitive inhibition by L-palmitoyl carnitine (inhibitory constant of 12 microM). Although lysophospholipase-transacylase activity could not be detected in rat myocyte or mesenchymal cell cultures, rabbit myocytes isolated by perfusion of isolated hearts with collagenase contained lysophospholipase-transacylase in cytosolic extracts with a specific activity of 0.2 nmol X mg-1 X min-1. These results demonstrate the presence of lysophospholipase in cardiac myocytes and suggest that the increase in long-chain acyl carnitine, which occurs during myocardial ischemia, may contribute to accumulation of lysophosphatides within cardiac myocytes.
D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives*; D055598:Chemical Phenomena; D002621:Chemistry; D003600:Cytosol / Q000201:enzymology*; D008245:Lysophospholipase / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D010740:Phospholipases / Q000032:analysis*; D011817:Rabbits; D051381:Rats
D010172:Palmitoylcarnitine; D010740:Phospholipases; D008245:Lysophospholipase; D002331:Carnitine