Mock T, Man R Y
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
Biochim Biophys Acta. 1991 Jul 9;1084(2):167-72. doi: 10.1016/0005-2760(91)90216-5.
Lysophosphatidylcholine (lysoPC) is an arrhythmogenic phospholipid metabolite which accumulates in the ischemic myocardium. Reduced catabolism of lysoPC has been proposed to be one of the biochemical mechanisms responsible for the increase in lysoPC content. In this investigation we compared the microsomal catabolism of exogenous labeled lysoPC in isolated perfused rat and guinea pig hearts. Analysis of the amount of radioactivity in microsomal phosphatidylcholine (PC) and free fatty acid (FFA) was used as an index of the participation in lysoPC clearance by acylation catalyzed by acyl-CoA:lysoPC acyltransferase and deacylation catalyzed by lysophospholipase, respectively. There was no significant difference in the incorporation of radioactivity into rat and guinea pig heart microsomes; however, the patterns of radioactivity in lysoPC metabolites were notably different. Equal participation by deacylation and reacylation was observed in rat microsomes, whereas deacylation was clearly the preferred route for lysoPC clearance in guinea pig microsomes. Modulation of enzyme activity by treatment of the isolated heart with pHMB, a sulfhydryl agent, was used to probe the relationship among acylation, deacylation and the extent of lysoPC clearance. In guinea pig microsomes impairment of lysoPC acylation was not associated with any change in the amount of radioactivity in lysoPC because of a compensatory increase in deacylation. In contrast, impaired deacylation in rat microsomes led to significant elevations in the amount of radioactivity in lysoPC. We conclude, therefore, that in intact perfused rat and guinea pig hearts the relative participation of acylation and deacylation in lysoPC clearance differs. Moreover, we propose that the level of deacylation by lysophospholipase is an important factor in the extent of clearance of lysoPC.
溶血磷脂酰胆碱（lysoPC）是一种致心律失常的磷脂代谢产物，在缺血心肌中会蓄积。lysoPC分解代谢减少被认为是导致lysoPC含量增加的生化机制之一。在本研究中，我们比较了外源性标记的lysoPC在离体灌注大鼠和豚鼠心脏中的微粒体分解代谢情况。分别以微粒体磷脂酰胆碱（PC）和游离脂肪酸（FFA）中的放射性量分析作为酰基辅酶A：lysoPC酰基转移酶催化的酰化作用以及溶血磷脂酶催化的脱酰作用参与lysoPC清除的指标。放射性掺入大鼠和豚鼠心脏微粒体中的情况无显著差异；然而，lysoPC代谢产物中的放射性模式明显不同。在大鼠微粒体中观察到脱酰作用和再酰化作用的参与程度相当，而在豚鼠微粒体中，脱酰作用显然是lysoPC清除的首选途径。用巯基试剂pHMB处理离体心脏以调节酶活性，以此探究酰化、脱酰作用与lysoPC清除程度之间的关系。在豚鼠微粒体中，lysoPC酰化作用受损并未伴随lysoPC中放射性量的任何变化，因为脱酰作用有代偿性增加。相反，大鼠微粒体中脱酰作用受损导致lysoPC中放射性量显著升高。因此，我们得出结论，在完整的灌注大鼠和豚鼠心脏中，酰化和脱酰作用在lysoPC清除中的相对参与程度不同。此外我们提出，溶血磷脂酶的脱酰水平是lysoPC清除程度的一个重要因素。
