ROLE OF IRON, HYDROGEN-PEROXIDE AND REACTIVE OXYGEN SPECIES IN MICROSOMAL OXIDATION OF GLYCEROL TO FORMALDEHYDE
ROLE OF IRON, HYDROGEN-PEROXIDE AND REACTIVE OXYGEN SPECIES IN MICROSOMAL OXIDATION OF GLYCEROL TO FORMALDEHYDE
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DOI：
10.1016/0003-9861(91)90331-c
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发表时间：
1991-02-15
影响因子：
3.9
通讯作者：
CEDERBAUM, AI
中科院分区：
文献类型：
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作者：
CLEJAN, LA;CEDERBAUM, AI
大鼠肝微粒体可将甘油氧化为甲醛。这种氧化是敏感的过氧化氢酶和谷胱甘肽加谷胱甘肽过氧化物酶，这表明在甘油氧化的整体途径中的H2O2的要求。过氧化氢不能代替NADPH支持甘油氧化，但添加H2O2可提高NADPH依赖性速率。氯化铁或铁ATP对甘油氧化没有影响，而铁EDTA是抑制性的。某些铁螯合剂，如去铁胺，EDTA或二亚乙基三胺五乙酸，但不是其他如ADP或柠檬酸盐，抑制甘油氧化。去铁胺的抑制作用可以通过添加铁来克服。无论是超氧化物歧化酶，也没有羟基自由基清除剂对甘油氧化有任何影响。除没食子酸丙酯外，几种抑制脂质过氧化的抗氧化剂对甘油产生甲醛没有影响。没食子酸丙酯的抑制作用可通过添加铁来克服。与甘油相反，从二甲基亚硝胺的甲醛生产是不敏感的过氧化氢酶或铁螯合剂，从而解离的甘油氧化从典型的混合功能氧化酶活性的细胞色素P450的整体途径。这些研究表明，H2O2和非血红素铁所需的甘油氧化为甲醛。负责任的氧化剂不是超氧化物、H2O2或羟基自由基。细胞色素P450可能具有产生H2O2和还原非血红素铁的功能。P450可能有其他作用，因为微粒体产生甲醛的速率超过了模型化学系统的速率。某些P450同工酶产生H2O2的速率升高，例如，P450 IIE1，可能有助于提高甘油氧化速率。
Rat liver microsomes can oxidize glycerol to formaldehyde. This oxidation is sensitive to catalase and glutathione plus glutathione peroxidase, suggesting a requirement for H2O2in the overall pathway of glycerol oxidation. Hydrogen peroxide can not replace NADPH in supporting glycerol oxidation; however, added H2O2increased the NADPH-dependent rate. Ferric chloride or ferric-ATP had no effect on glycerol oxidation, whereas ferric-EDTA was inhibitory. Certain iron chelators such as desferrioxamine, EDTA or diethylenetriaminepentaacetic acid, but not others such as ADP or citrate, inhibited glycerol oxidation. The inhibition by desferrioxamine could be overcome by added iron. Neither superoxide dismutase nor hydroxyl radical scavengers had any effect on glycerol oxidation. With the exception of propyl gallate, several antioxidants which inhibit lipid peroxidation had no effect on formaldehyde production from glycerol. The inhibition by propyl gallate could be overcome by added iron. In contrast to glycerol, formaldehyde production from dimethylnitrosamine was not sensitive to catalase or iron chelators, thus disassociating the overall pathway of glycerol oxidation from typical mixed-function oxidase activity of cytochrome P450. These studies indicate that H2O2and nonheme iron are required for glycerol oxidation to formaldehyde. The responsible oxidant is not superoxide, H2O2, or hydroxyl radical. Cytochrome P450 may function to generate the H2O2and reduce the nonheme iron. There may be additional roles for P450 since rates of formaldehyde production by microsomes exceed rates found with model chemical systems. Elevated rates of H2O2production by certain P450 isozymes, e.g., P450 IIE1, may contribute to enhanced rates of glycerol oxidation.