Wientzek M, Man R Y, Choy P C
Department of Biochemistry, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Biochem Cell Biol. 1987 Oct;65(10):860-8. doi: 10.1139/o87-112.
The aims of this study were to (i) elucidate the biosynthetic pathways for the formation of plasmenylcholine in the mammalian heart and (ii) investigate whether the control of choline glycerophospholipid production is different in hearts with high plasmenylcholine content. Guinea pig hearts were used throughout this study, since 34% of the cardiac choline glycerophospholipids in this species is present in the plasmenylcholine form. By perfusion of the guinea pig heart in the Langendorff mode with labeled choline, we demonstrated that the majority of plasmenylcholine in the heart was synthesized via the CDP-choline pathway. The ability of the heart to form plasmenylcholine from CDP-choline and 1-alkenyl-2-acylglycerol was also shown. We postulate that 1-alkenyl-2-acylglycerol in the guinea pig heart might originate from the hydrolysis of plasmenylethanolamine. In mammalian liver and other tissues, the CDP-choline pathway is the major pathway for phosphatidylcholine biosynthesis and the rate-limiting step is catalyzed by CTP:phosphocholine cytidylyltransferase. The results obtained from the present study support this supposition. In addition, evidence was obtained indicating that phosphorylation of choline by choline kinase in the CDP-choline pathway may also be rate limiting. Although the involvement of choline kinase as a rate-limiting enzyme in the CDP-choline pathway has been shown in a number of cell cultures, the rate-limiting role of this enzyme in intact mammalian organs has not been previously reported. The rationale for the presence of more than one rate-limiting step in the CDP-choline pathway in the guinea pig heart remains undefined.
(i)阐明哺乳动物心脏中缩醛磷脂酰胆碱形成的生物合成途径;(ii)研究缩醛磷脂酰胆碱含量高的心脏中胆碱甘油磷脂生成的调控是否存在差异。在整个研究过程中使用了豚鼠心脏,因为该物种心脏中34%的胆碱甘油磷脂以缩醛磷脂酰胆碱的形式存在。通过在Langendorff模式下用标记的胆碱灌注豚鼠心脏,我们证明心脏中的大部分缩醛磷脂酰胆碱是通过CDP-胆碱途径合成的。还展示了心脏从CDP-胆碱和1-烯基-2-酰基甘油形成缩醛磷脂酰胆碱的能力。我们推测豚鼠心脏中的1-烯基-2-酰基甘油可能源自缩醛磷脂酰乙醇胺的水解。在哺乳动物肝脏和其他组织中,CDP-胆碱途径是磷脂酰胆碱生物合成的主要途径,限速步骤由CTP:磷酸胆碱胞苷转移酶催化。本研究获得的结果支持这一推测。此外,有证据表明CDP-胆碱途径中胆碱激酶对胆碱的磷酸化作用也可能是限速的。尽管胆碱激酶作为CDP-胆碱途径中的限速酶在许多细胞培养中已有报道,但该酶在完整哺乳动物器官中的限速作用此前尚未见报道。豚鼠心脏中CDP-胆碱途径存在多个限速步骤的原因仍不明确。