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离体大鼠肝线粒体中溶血心磷脂的形成与再酰化作用

Lysocardiolipin formation and reacylation in isolated rat liver mitochondria.

作者信息

Schlame M, Rüstow B

机构信息

Institute of Physical Biochemistry, University of Munich, Federal Republic of Germany.

出版信息

Biochem J. 1990 Dec 15;272(3):589-95. doi: 10.1042/bj2720589.

DOI:10.1042/bj2720589
PMID:2268287
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1149749/
Abstract

Liver mitochondrial cardiolipin (CL) is distinguished from other phospholipids by the presence of linoleoyl in almost all molecular species, and the biosynthesis of these species is not yet understood. The present study was carried out in order to test the hypothesis that the linoleoyl proportion of CL may be specifically enriched by a deacylation-reacylation cycle. Incorporation of [14C]glycerol 3-phosphate into the metabolites of the CL pathway was accompanied by formation of 14C-labelled monolyso- and dilyso-CL. Labelling of dilyso-CL was increased or decreased by stimulation or inhibition respectively of mitochondrial phospholipase A2. These data suggest a rapid deacylation of newly formed [14C]CL by phospholipase A2, whereas endogenous mitochondrial CL was very resistant to hydrolytic degradation. Unlike dilyso-CL, monolyso-CL could be reacylated by [14C]linoleoyl residues. [14C]Linoleoyl incorporation into CL was also observed when exogenous CL was added instead of monolyso-CL, thus indicating the concerted action of de- and re-acylation. Although 1-palmitoyl-2-[14C]linoleoyl-phosphatidylcholine was a suitable acyl donor under experimental conditions, the reaction was not a transacylation but required splitting of [14C]linoleic acid from phosphatidylcholine and formation of [14C]linoleoyl-CoA as an intermediate. The [14C]linoleoyl was mainly bound to the sn-2(2") position of CL, and a small portion (about 20%) to the sn-1(1") position. It is concluded that a cycle, comprising CL deacylation and monolyso-CL reacylation by linoleoyl-CoA, provides a potential mechanism for the remodelling of molecular species of newly formed CL.

摘要

肝脏线粒体心磷脂(CL)与其他磷脂的区别在于几乎所有分子种类中都存在亚油酰基,而这些种类的心磷脂的生物合成尚不清楚。进行本研究是为了检验这样一个假设,即CL的亚油酰基比例可能通过脱酰基-再酰基化循环而特异性富集。[14C]甘油3-磷酸掺入CL途径的代谢产物伴随着14C标记的单溶血和双溶血CL的形成。分别通过刺激或抑制线粒体磷脂酶A2,双溶血CL的标记增加或减少。这些数据表明,新形成的[14C]CL被磷脂酶A2快速脱酰基,而内源性线粒体CL对水解降解具有很强的抗性。与双溶血CL不同,单溶血CL可以被[14C]亚油酰基残基再酰基化。当添加外源CL而非单溶血CL时,也观察到[14C]亚油酰基掺入CL,从而表明脱酰基和再酰基化的协同作用。尽管1-棕榈酰-2-[14C]亚油酰基磷脂酰胆碱在实验条件下是合适的酰基供体,但该反应不是转酰基反应,而是需要将[14C]亚油酸从磷脂酰胆碱中裂解出来并形成[14C]亚油酰辅酶A作为中间体。[14C]亚油酰基主要结合在CL的sn-2(2")位置,一小部分(约20%)结合在sn-1(1")位置。得出的结论是,由CL脱酰基和亚油酰辅酶A对单溶血CL再酰基化组成的循环为新形成的CL分子种类的重塑提供了一种潜在机制。

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