OXIDATION OF ACETALDEHYDE BY ISOLATED-MITOCHONDRIA FROM VARIOUS ORGANS OF RAT AND HEPATOCELLULAR CARCINOMA
OXIDATION OF ACETALDEHYDE BY ISOLATED-MITOCHONDRIA FROM VARIOUS ORGANS OF RAT AND HEPATOCELLULAR CARCINOMA
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DOI：
10.1016/0003-9861(77)90085-6
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发表时间：
1977-01-01
影响因子：
3.9
通讯作者：
RUBIN, E
中科院分区：
文献类型：
--
作者：
CEDERBAUM, AI;RUBIN, E
肝、肾、脑和骨骼肌的线粒体代谢乙醛。肝脏和肾脏线粒体的乙醛氧化在低水平乙醛下最大，并且对鱼藤酮敏感，表明参与了对乙醛具有高亲和力的NAD+依赖性醛脱氢酶[EC 1.2.1.3]。ADP刺激乙醛氧化50%，这表明，在状态4中，NADH的再氧化是乙醛氧化的速率限制。在状态4，乙醛氧化减少NAD+依赖性底物，琥珀酸和抗坏血酸。ADP、二硝基苯酚、缬氨霉素和短杆菌肽能抑制后两种底物的抑制作用，寡霉素则不能。由于这些化合物与能量转导和利用有关，因此抑制作用可能是通过能量依赖性的反向电子传递介导的。在状态3中，所有这些底物对乙醛氧化的抑制作用显著降低，表明乙醛脱氢酶的活性而不是NADH再氧化可能是乙醛氧化的速率限制。离子载体缬氨霉素和短杆菌肽刺激乙醛氧化在更大程度上比ADP。这些离子载体也刺激乙醛氧化在ADP的存在下。缬氨霉素的刺激发生在由该离子载体转运的单价阳离子的存在下，例如，K+、Rb+、Cs+。短杆菌肽的刺激也发生在这些阳离子的存在下，但没有发生与Na+或LI+。Na+阻止乙醛氧化的刺激，乙醛氧化在短杆菌肽和K+存在下发生。缬氨霉素和短杆菌肽的刺激是能量依赖性的，需要渗透阴离子的存在。在没有离子载体的情况下，磷酸钾对乙醛氧化没有影响。大鼠肝、肾线粒体对乙醛的氧化可能受线粒体氧化还原状态和阳离子环境的影响。与脑和肌肉线粒体，乙醛氧化的速率增加2至3倍，乙醛的浓度从0.167至0.50 mM。乙醛氧化在这些线粒体也是敏感的鱼藤酮，指示依赖于NAD+。ADP，缬氨霉素，短杆菌肽和琥珀酸，化合物，增加或减少乙醛氧化率的肝和肾线粒体，对乙醛氧化的肌肉或脑线粒体没有影响。在状态4中，来自贝克尔可移植肝细胞癌HC-252的线粒体以与肝线粒体相同的速率氧化乙醛。在ADP、二硝基苯酚、缬氨霉素和短杆菌肽存在下，肿瘤线粒体对乙醛的氧化速率比肝线粒体快2-3倍，表明肿瘤线粒体存在比肝线粒体更活跃的乙醛还原系统。
Mitochondria from liver, kidney, brain and skeletal muscle metabolized acetaldehyde. Acetaldehyde oxidation by liver and kidney mitochondria was maximal at low levels of acetaldehyde and was sensitive to rotenone, suggesting the involvement of a NAD+-dependent aldehyde dehydrogenase [EC 1.2.1.3] with a high affinity for acetaldehyde. Acetaldehyde oxidation was stimulated 50% by ADP, suggesting that, in state 4, reoxidation of NADH is rate limiting for acetaldehyde oxidation. In state 4, acetaldehyde oxidation was decreased by NAD+-dependent substrates, and by succinate and ascorbate. The inhibition by the latter 2 substrates was prevented by ADP, dinitrophenol, valinomycin and gramicidin, but not by oligomycin. Since these compounds are linked to energy transduction and utilization, the inhibition is probably mediated via energy-dependent reversed electron transport. In state 3, all of these substrates caused considerably less inhibition of acetaldehyde oxidation, suggesting that the activity of aldehyde dehydrogenase, and not NADH reoxidation, is probably rate limiting for acetaldehyde oxidation. The ionophores valinomycin and gramicidin stimulated acetaldehyde oxidation to a greater extent than ADP. These ionophores also stimulated acetaldehyde oxidation in the presence of ADP. Stimulation by valinomycin occurred in the presence of monovalent cations transported by this ionophore, e.g., K+, Rb+, Cs+. Stimulation by gramicidin also occurred in the presence of these cations, but did not occur with Na+ or LI+. Na+ prevents the stimulation of acetaldehyde oxidation, which occurs in the presence of gramicidin and K+. Stimulation by valinomycin and gramicidin was energy dependent and required the presence of a permeant anion. In the absence of an ionophore, potassium phosphate had no effect on acetaldehyde oxidation. The oxidation of acetaldehyde by rat liver and kidney mitochondria may be influenced by the oxidation-reduction state of the mitochondria and the cationic environment. With brain and muscle mitochondria, the rate of acetaldehyde oxidation increased 2- to 3-fold as the concentration of acetaldehyde was raised from 0.167 to 0.50 mM. Acetaldehyde oxidation in these mitochondria was also sensitive to rotenone, indication dependence on NAD+. ADP, valinomycin, gramicidin and succinate, compounds which increased or decreased the rate of acetaldehyde oxidation by liver and kidney mitochondria, had no effect on acetaldehyde oxidation by muscle or brain mitochondria. In state 4, mitochondria from Becker transplantable hepatocellular carcinoma HC-252 oxidized acetaldehyde at the same rate as liver mitochondria. In the presence of ADP, dinitrophenol, valinomycin and gramicidin, the rate of acetaldehyde oxidation by the tumor mitochondria was 2-3 times greater than that of liver mitochondria, suggesting the presence of a more active acetaldehyde-oxidizing system in tumor than in liver mitochondria.