Choy P C
J Biol Chem. 1982 Sep 25;257(18):10928-33.
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.
本实验室之前的一份报告表明，仓鼠心脏中的大部分磷脂酰胆碱是通过CDP-胆碱途径由胆碱形成的（泽林斯基，T.A.，萨瓦德，J.D.，曼，R.Y.K.，和蔡，P.C.（1980年）《生物化学杂志》255卷，11423 - 11428页）。在本研究中，将患肌病仓鼠心脏中的磷脂酰胆碱生物合成与年龄匹配的对照进行了比较。用[甲基-³H]胆碱灌注后，在150 - 200日龄患肌病仓鼠的心脏中观察到磷脂酰胆碱的标记增加了22%。然而，心脏中总的磷脂酰胆碱含量保持不变。为了阐明心肌病期间磷脂酰胆碱标记增加的原因，对患肌病心脏中磷脂酰胆碱形成的中间体进行了分析。发现患肌病心脏中CDP-胆碱的标记和池大小分别为对照的72%和60%。这种不均衡的减少导致CDP-胆碱的比放射性增加了20%。由于CDP-胆碱是磷脂酰胆碱形成的直接前体，可以得出结论，患肌病心脏中磷脂酰胆碱标记的增加是CDP-胆碱比放射性的直接反映。此外，估计正常心脏和患肌病心脏之间合成的磷脂酰胆碱净量相似。CDP-胆碱形成的减少可能是由于在心肌病中观察到的CTP浓度降低所致。然而，磷酸胆碱胞苷转移酶活性升高。增强的酶活性被认为是患肌病心脏维持最低CDP-胆碱水平以防止磷脂酰胆碱生物合成净量减少的代偿机制之一。
