Pyruvate Metabolism
Pyruvate Metabolism
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DOI：
10.1016/s0021-9258(18)64656-3
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发表时间：
2003
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影响因子：
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通讯作者：
O. Reiss
中科院分区：
文献类型：
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作者：
O. Reiss
结合本实验室丙酮酸代谢 (3) 的研究，大鼠心脏肌小体制剂已被描述为在适当的条件下代谢丙酮酸并同时产生大量柠檬酸 (1)。在几种选定的抑制剂存在下，对此类制剂中丙酮酸消失和柠檬酸形成速率的观察表明，其中一种抑制剂，γ-(对砷基苯基)-丁酸，可用于对该过程建立高效的阻断，而第二种抑制物质，对氯汞苯甲酸酯，则效果较差。后一种试剂的作用被单硫醇如谷胱甘肽或半胱氨酸阻止，但砷化合物的抑制作用在这些试剂中的任一种存在下不受影响。这些结果指出了砷化合物攻击的一个相当具体的部位。观察到二硫醇，6,% 二巯基辛酸（二氢硫辛酸），已知是细菌丙酮酸氧化系统中的辅助因子 (4)，可以轻松有效地逆转砷基苯丁酸的抑制作用，事实上比 2, 3-二巯基丙醇更完全，后者确实被发现对 有关的酶系统。进一步观察发现，添加氧化形式的 cr-(+)-硫辛酸（硫辛酸）代替二氢硫辛酸，也恢复了砷抑制系统的活性，从而得出这样的假设：该辅助因子可能在大鼠心脏肌小体中发挥重要作用，可能类似于其在某些非哺乳动物系统中的功能。这些观察结果在本通讯中得到扩展，进一步证明了硫辛酸氧化形式所描述的再活化作用是立体定向的，在这种情况下，砷基苯基化合物对有氧丙酮酸利用的抑制的缓解仅是环硫辛酸的去旋异构体的性质，
In connection with investigations of pyruvate metabolism (3) in this laboratory, preparations of rat heart sarcosomes have been described that under suitable conditions metabolize pyruvate and concomitantly produce large amounts of citrate (1). Observation of the rate of pyruvate disappearance and citrate formation in such preparations, in the presence of several selected inhibitors, disclosed that one of these inhibitors, y-(p-arsenosophenyl)-nbutyrate, could be used to institute a highly effective block for this process, whereas a second inhibiting substance, p-chloromercuribenzoate, was less effective. The action of the latter agent was prevented by monothiols such as glutathionc or cysteine, but inhibition by the arsenoso compound was not affected in the presence of either of these reagents. Such results pointed to a rather specific site of attack by the arsenoso compound. This view was strengthened by the observation that the dithiol, 6,% dimercaptooctanoic(dihydrolipoic) acid, known to be a cofactor in the bacterial pyruvate oxidation system (4), readily and effectively reversed the inhibition by the arsenosophenylbutyrate, more completely in fact than 2, 3-dimercaptopropanol, which indeed was found to be somewhat inhibitory to the enzyme system concerned. The further observation that the addition of the oxidized form of cr-(+)-lipoic acid (thioctic acid), in place of dihydrolipoate, also restored activity in the arsenoso-inhibited system led to the postulation that this cofactor might be playing an essential role in rat heart sarcosomes possibly similar to its function in certain nonmammalian systems. These observations are extended in the present communication with the additional demonstration that the reactivation effect described for the oxidized form of lipoic acid is stereospecific, in the sense that relief of the inhibition of aerobic pyruvate utilization in this instance by the arsenosophenyl compound is a property only of the destrorotatory isomer of cy-lipoic acid, the