Rustenbeck I, Lenzen S
Institute of Pharmacology and Toxicology, University of Göttingen, F.R.G.
Biochim Biophys Acta. 1989 Jun 26;982(1):147-55. doi: 10.1016/0005-2736(89)90185-5.
The effects of arachidonic acid and other fatty acids on mitochondrial Ca2+ transport were studied. Cis-unsaturated fatty acids generally strongly inhibited mitochondrial Ca2+ uptake, induced a net Ca2+ efflux, and thereby increased the extramitochondrial Ca2+ concentration, whereas trans-unsaturated fatty acids were ineffective. Saturated fatty acids exhibited slight activity at chain lengths from C(10) to C(14) only. The structure-activity relationship and the inability of some of the effective fatty acids such as palmitoleic and myristoleic acid to be metabolized to eicosanoids suggest that Ca2+ release was induced by the fatty acids themselves and resulted from changes in the mitochondrial membrane bilayer structure. There was a correlation between Ca2+-releasing potency and reduction of mitochondrial membrane potential, which is the main driving force for mitochondrial Ca2+ uptake. There were, however, considerable differences compared with the effects of lysophospholipids on the membrane potential. The mechanism of action of fatty acids may be that of a fluidizing effect on the hydrophobic core of the membrane, thereby modulating the activity of integral membrane proteins of the respiratory chain.
研究了花生四烯酸和其他脂肪酸对线粒体钙转运的影响。顺式不饱和脂肪酸通常强烈抑制线粒体对钙的摄取，诱导净钙外流，从而增加线粒体外钙浓度，而反式不饱和脂肪酸则无效。饱和脂肪酸仅在碳链长度为C(10)至C(14)时表现出轻微活性。结构-活性关系以及一些有效脂肪酸（如棕榈油酸和肉豆蔻油酸）无法代谢为类二十烷酸表明，钙释放是由脂肪酸本身诱导的，并且是线粒体膜双层结构变化的结果。钙释放能力与线粒体膜电位降低之间存在相关性，而线粒体膜电位是线粒体摄取钙的主要驱动力。然而，与溶血磷脂对膜电位的影响相比，存在相当大的差异。脂肪酸的作用机制可能是对膜疏水核心产生流化作用，从而调节呼吸链整合膜蛋白的活性。
