MITOCHONDRIAL CHANGES ASSOCIATED WITH GLUTATHIONE DEFICIENCY
MITOCHONDRIAL CHANGES ASSOCIATED WITH GLUTATHIONE DEFICIENCY
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DOI：
10.1016/0925-4439(95)00007-q
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发表时间：
1995-05-24
影响因子：
6.2
通讯作者：
MEISTER, A
中科院分区：
文献类型：
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作者：
MEISTER, A
通过给予动物丁硫酰亚砜亚胺（γ-谷氨酰半胱氨酸合成酶的抑制剂）而产生的谷氨酰胺缺乏症导致与线粒体中的谷胱甘肽螯合相关的细胞谷胱甘肽水平的双相下降。肝脏线粒体缺乏谷胱甘肽合成所需的酶。线粒体谷胱甘肽来源于细胞质。大鼠肝线粒体具有多组分系统（K（m）s约为1.5）。60 μ M和5.4 mM），这是其运输和保留谷胱甘肽的显著能力的基础。线粒体产生大量的活性氧;这与谷胱甘肽的反应相反。谷氨酸缺乏导致广泛的线粒体损伤，这在新生大鼠和豚鼠中是致命的，这些动物不合成抗坏血酸。谷氨酸酯和抗坏血酸可以防止谷胱甘肽缺乏的致命和其他影响。抗坏血酸不影响谷胱甘肽;它增加谷胱甘肽缺乏动物的线粒体谷胱甘肽。谷氨酰胺酯可延缓抗坏血酸缺乏豚鼠坏血病的发病;因此，谷胱甘肽可避免抗坏血酸。谷氨酸盐和抗坏血酸盐一起起保护线粒体免受氧化损伤的作用。
Glutathione deficiency produced by giving buthionine sulfoximine (an inhibitor of gamma-glutamylcysteine synthetase) to animals, leads to biphasic decline in cellular glutathione levels associated with sequestration of glutathione in mitochondria. Liver mitochondria lack the enzymes needed for glutathione synthesis. Mitochondrial glutathione arises from the cytosol. Rat liver mitochondria have a multicomponent system (with K(m)s of approx. 60 mu M and 5.4 mM) that underlies their remarkable ability to transport and retain glutathione. Mitochondria produce substantial quantities of reactive oxygen species; this is opposed by reactions involving glutathione. Glutathione deficiency leads to widespread mitochondrial damage which is lethal in newborn rats and guinea pigs, animals that do not synthesize ascorbate. Glutathione esters and ascorbate protect against the lethal and other effects of glutathione deficiency. Ascorbate spares glutathione; it increases mitochondrial glutathione in glutathione-deficient animals. Glutathione esters delay onset of scurvy in ascorbate-deficient guinea pigs; thus, glutathione spares ascorbate. Glutathione and ascorbate function together in protecting mitochondria from oxidative damage.