Zinc causes a shift toward citrate at equilibrium of the m-aconitase reaction of prostate mitochondria
Zinc causes a shift toward citrate at equilibrium of the m-aconitase reaction of prostate mitochondria
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DOI：
10.1016/s0162-0134(99)00225-1
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发表时间：
2000-01-30
影响因子：
3.9
通讯作者：
Kennedy, MC
中科院分区：
文献类型：
--
作者：
Costello, LC;Franklin, RB;Kennedy, MC
前列腺分泌上皮细胞具有积累和分泌极高水平柠檬酸盐的独特功能和能力。为了实现这一目标，这些细胞具有独特的限制性线粒体 (m)-乌头酸酶活性，可最大限度地减少三羧酸循环中柠檬酸的氧化。哺乳动物组织的稳态柠檬酸盐/异柠檬酸盐比率通常维持在约10-11/1，与柠檬酸盐的浓度无关，这是在间乌头酸酶存在下达到化学平衡的结果。相反，前列腺组织的柠檬酸盐/异柠檬酸盐比率约为30-40/1。锌在前列腺细胞中的积累水平也比其他细胞高得多，它抑制 m-乌头酸酶活性，从而最大限度地减少柠檬酸盐氧化。本报告涉及锌对间乌头酸酶催化反应平衡的影响。使用大鼠腹侧前列腺上皮细胞的线粒体提取物制剂进行了研究。以柠檬酸盐作为初始底物，向前列腺线粒体制剂中添加锌（7-10μM）导致平衡状态下柠檬酸盐/异柠檬酸盐比率从平均10.5/1变化至13.5/1。相比之下，对肾线粒体制剂进行相同的处理没有导致锌诱导的柠檬酸盐/异柠檬酸盐比率的变化。当使用顺乌头酸盐或异柠檬酸盐作为初始底物时，添加锌不会改变前列腺或肾脏制剂的柠檬酸盐/异柠檬酸盐比率。前列腺制剂的部分纯化表明，前列腺线粒体提取物含有一种假定的蛋白质（我们将其命名为“柠檬酸盐因子蛋白质”），该蛋白质是锌诱导的柠檬酸盐/异柠檬酸盐比率增加所必需的。锌的这种新作用提供了另一种机制，通过该机制可以确保柠檬酸盐在产生柠檬酸盐的前列腺上皮细胞中的积累最大化。 (C) 2000 Elsevier Science Inc. 保留所有权利。
Prostate secretory epithelial cells have the unique function and capability of accumulating and secreting extraordinarily high levels of citrate. To achieve this, these cells possess a uniquely limiting mitochondrial (m)-aconitase activity that minimizes the oxidation of citrate via the Krebs cycle. The steady-state citrate/isocitrate ratio of mammalian tissues is generally maintained at about 10-11/1, independent of the concentration of citrate, which is the result of the chemical equilibrium reached in the presence of m-aconitase. In contrast, the citrate/isocitrate ratio of prostate tissue is about 30-40/1. Zinc, which is also accumulated in prostate cells at much higher levels than in other cells, inhibits m-aconitase activity thereby minimizing citrate oxidation. This current report is concerned with an effect of zinc on the equilibrium of the reaction catalyzed by m-aconitase. Studies were conducted with mitochondrial extract preparations from rat ventral prostate epithelial cells. With citrate as the initial substrate, the addition of zinc (7-10 mu M) to the prostate mitochondrial preparation resulted in a change in the citrate/isocitrate ratio at equilibrium from an average of 10.5/1 to 13.5/1. In contrast, the identical treatment of kidney mitochondrial preparations resulted in no zinc-induced change in the citrate/isocitrate ratio. When either cis-aconitate or isocitrate was employed as the initial substrate, the addition of zinc did not alter the citrate/isocitrate ratio of prostate or kidney preparations. Partial purification of the prostate preparation revealed that the prostate mitochondrial extract contained a putative protein (which we have designated as 'citrate factor protein') that is required for the zinc-induced increase in the citrate/isocitrate ratio. This novel effect of zinc provides another mechanism by which it is assured that the accumulation of citrate is maximized in citrate-producing prostate epithelial cells. (C) 2000 Elsevier Science Inc. All rights reserved.