Control of phosphatidylcholine biosynthesis in myopathic hamster hearts.
A previous report from this laboratory demonstrated that the majority of phosphatidylcholine in hamster heart was formed from choline via the CDP-choline pathway (Zelinski, T. A., Savard, J. D., Man, R. Y. K., and Choy, P. C. (1980) J. Biol. Chem. 255, 11423-11428). In this study, phosphatidylcholine biosynthesis in myopathic hamster hearts was compared with date-matched controls. Upon perfusion with [Me-3H]choline, a 22% increase in labeling of phosphatidylcholine was observed in the hearts of 150-200-day-old myopathic hamsters. However, total cardiac phosphatidylcholine remained unchanged. In order to elucidate the cause for the increase in labeling of phosphatidylcholine during cardiomyopathy, the intermediates for phosphatidylcholine formation in the myopathic hearts were analyzed. The labeling and pool size of CDP-choline in the myopathic hearts were found to be 72 and 60% of the controls. This uneven reduction caused a 20% increase in the specific radioactivity of CDP-choline. Since CDP-choline is the immediate precursor for phosphatidylcholine formation, it can be concluded that the increase in labeling of phosphatidylcholine in the myopathic heart was a direct reflection on the specific radioactivity of CDP-choline. Furthermore, the net amount of phosphatidylcholine synthesized was estimated to be similar between the normal and myopathic hearts. The reduction in CDP-choline formation was probably caused by an observed decrease in CTP concentration in cardiomyopathy. However, phosphocholine cytidylyltransferase activity was elevated. The enhanced enzyme activity is regarded as one of the compensatory mechanism for the myopathic heart to maintain a minimum CDP-choline level, in order to prevent reduction of net phosphatidylcholine biosynthesis.
D000375:Aging; D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D006224:Cricetinae; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D003570:Cytidine Triphosphate / Q000378:metabolism; D006321:Heart / Q000254:growth & development; D007700:Kinetics; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D012016:Reference Values
D010713:Phosphatidylcholines; D003566:Cytidine Diphosphate Choline; D003570:Cytidine Triphosphate; D002794:Choline