Effects of disulfiram on the oxidation of benzaldehyde and acetaldehyde in rat liver.
Effects of disulfiram on the oxidation of benzaldehyde and acetaldehyde in rat liver.
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双硫仑对大鼠肝脏苯甲醛和乙醛氧化的影响。
DOI：
10.1016/0006-2952(85)90695-1
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发表时间：
1985
影响因子：
5.8
通讯作者：
Weiner,H
中科院分区：
文献类型：
--
作者：
Hellström-Lindahl,E;Weiner,H
在双硫仑处理和对照大鼠的肝脏样品中研究了苯甲醛和乙醛的体外氧化。当底物浓度为25 μM时，细胞质和线粒体对苯甲醛氧化的贡献几乎相等，而乙醛氧化约90%发生在线粒体中。当测定苯甲醛与乙醛脱氢酶（ALDH）的Km值时，线粒体得到两个Km值（3和120 μM），而胞浆部分只得到一个Km值（25 μM）。微粒体的Km值相对较高（2.9 mM），因此微粒体在苯甲醛氧化中不太可能起重要作用。在完整的线粒体中，200 μM乙醛或苯甲醛的基质空间酶分别占总ALDH活性的77%和62%。当在含有两种底物的混合物中测定活性时，发现活性不是加和的，表明两种底物被相同的基质空间酶氧化。与亚细胞组分，从双硫仑治疗和对照大鼠的肝脏，更大程度的抑制ALDH时，乙醛是一种底物相比，与苯甲醛在细胞质和线粒体。双硫仑不抑制微粒体ALDH。在给予双硫仑的大鼠肝切片中，当使用25或250 μM乙醛时，发现具有统计学显著性的抑制作用（46%和33%）。对于苯甲醛，仅在较低底物浓度下观察到显著抑制（24%）。发现线粒体组分和切片在较高的底物浓度下受到较少的抑制，这意味着高Kmenzyme不受抑制。因此，双硫仑抑制大鼠肝脏ALDH不仅影响乙醛的氧化，而且也影响苯甲醛的氧化。
Thein vitrooxidation of benzaldehyde and acetaldehyde was studied in liver samples from disulfiram-treated and control rats. With 25 μM substrate, both cytosol and mitochondria appeared to make a nearly equal contribution to the oxidation of benzaldehyde, whereasca.90% of acetaldhyde oxydation occurred in mitochondria. When theKmvalues for benzaldehyde with aldehyde dehydrogenase (ALDH) were determined, twoKmvalues (3 and 120 μM) were obtained with mitochondria, but only a singleKmvalue (25 μM) was obtained with the cytosolic fraction. The relatively highKm(2.9 mM) found with microsomes makes it unlikely that microsomes are important in the oxidation of benzaldehyde. In intact mitochondria, with 200 μM acetaldehyde or benzaldehyde the matrix space enzyme accounted for 77 and 62%, respectively, of the total ALDH activity. When the activity was determined in a mixture containing both substrates, the activity was found not to be additive, indicating that both substrates are oxidized by the same matrix space enzyme. With subcellular fractions, from livers of disulfiram-treated and control rats, a greater degree of inhibition of ALDH was obtained when acetaldehyde was a substrate compared to that with benzaldehyde in cytosol and mitochondria. Microsomal ALDH was not inhibited by disulfiram. In liver slices from rats given disulfiram, a statistically significant inhibition was found when either 25 or 250 μM acetaldehyde was used (46 and 33%). With benzaldehyde, a significant inhibition (24%) was observed only with the lower substrate concentration. Finding that both mitochondrial fractions and slices were less inhibited at the higher substrate concentration implies that the highKmenzyme is not inhibited. It can be concluded that, in rat, disulfiram inhibiting liver ALDH not only affects oxidation of acetaldehyde, but also that of benzaldehyde.