Schlame M, Greenberg M L
Dept. of Anesthesiology, Charite Hospital, Humboldt University, Berlin, Germany.
Biochim Biophys Acta. 1997 Sep 4;1348(1-2):201-6. doi: 10.1016/s0005-2760(97)00117-3.
Cardiolipin synthase catalyzes the synthesis of the mitochondrial phospholipid cardiolipin. Cardiolipin synthase is a unique membrane-bound enzyme in that it utilizes two phospholipids, both insoluble in water, as substrates. Kinetic analysis suggests that the enzyme forms a ternary complex with the two lipid substrates, and that a divalent metal ion directly associates with cardiolipin synthase to form the active enzyme. While little is known about the regulation of cardiolipin synthase in yeast, activity is reduced in mutants in which the mitochondrial genome is deleted, and in mutants with defective respiratory complexes. In p0 mutants, which contain no mitochondrial DNA and are defective in the assembly of many mitochondrial membrane protein complexes, cardiolipin synthase activity is reduced by 50%. Mutants defective in respiratory complexes, particularly those incapable of cytochrome oxidase assembly, also have reduced cardiolipin synthase activity. Thus it is likely that respiration and cardiolipin formation are interdependent. The enzyme was recently purified from the budding yeast Saccharomyces cerevisiae. Enzyme activity was associated with a 25-30-kDa protein. The amino acid sequence of this protein, combined with the availability of the complete yeast genome sequence, will hopefully lead to the identification of the structural gene for this enzyme in the near future.
心磷脂合酶催化线粒体磷脂心磷脂的合成。心磷脂合酶是一种独特的膜结合酶，因为它利用两种均不溶于水的磷脂作为底物。动力学分析表明，该酶与两种脂质底物形成三元复合物，并且二价金属离子直接与心磷脂合酶结合以形成活性酶。虽然对酵母中心磷脂合酶的调节了解甚少，但在缺失线粒体基因组的突变体以及呼吸复合物有缺陷的突变体中，其活性会降低。在不含线粒体DNA且许多线粒体膜蛋白复合物组装有缺陷的p0突变体中，心磷脂合酶活性降低了50%。呼吸复合物有缺陷的突变体，尤其是那些无法组装细胞色素氧化酶的突变体，心磷脂合酶活性也会降低。因此，呼吸作用和心磷脂形成可能是相互依赖的。该酶最近已从出芽酵母酿酒酵母中纯化出来。酶活性与一种25 - 30 kDa的蛋白质相关。这种蛋白质的氨基酸序列，结合完整的酵母基因组序列，有望在不久的将来鉴定出该酶的结构基因。
