Clejan L A, Cederbaum A I
Department of Biochemistry, Mount Sinai School of Medicine (CUNY), New York 10029.
Arch Biochem Biophys. 1991 Feb 15;285(1):83-9. doi: 10.1016/0003-9861(91)90331-c.
Rat liver microsomes can oxidize glycerol to formaldehyde. This oxidation is sensitive to catalase and glutathione plus glutathione peroxidase, suggesting a requirement for H2O2 in the overall pathway of glycerol oxidation. Hydrogen peroxide can not replace NADPH in supporting glycerol oxidation; however, added H2O2 increased 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 H2O2 and 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 H2O2 and 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 H2O2 production by certain P450 isozymes, e.g., P450 IIE1, may contribute to enhanced rates of glycerol oxidation.
大鼠肝脏微粒体可将甘油氧化为甲醛。这种氧化对过氧化氢酶、谷胱甘肽以及谷胱甘肽过氧化物酶敏感，这表明在甘油氧化的整个途径中需要过氧化氢。过氧化氢不能替代烟酰胺腺嘌呤二核苷酸磷酸（NADPH）来支持甘油氧化；然而，添加过氧化氢会提高NADPH依赖的反应速率。氯化铁或铁 - 三磷酸腺苷（ATP）对甘油氧化没有影响，而铁 - 乙二胺四乙酸（EDTA）具有抑制作用。某些铁螯合剂，如去铁胺、EDTA或二乙烯三胺五乙酸，但其他一些如二磷酸腺苷（ADP）或柠檬酸盐则不然，会抑制甘油氧化。去铁胺的抑制作用可通过添加铁来克服。超氧化物歧化酶和羟基自由基清除剂对甘油氧化均无任何影响。除了没食子酸丙酯外，几种抑制脂质过氧化的抗氧化剂对甘油生成甲醛没有影响。没食子酸丙酯的抑制作用可通过添加铁来克服。与甘油不同，二甲基亚硝胺生成甲醛对过氧化氢酶或铁螯合剂不敏感，因此将甘油氧化的整个途径与细胞色素P450典型的混合功能氧化酶活性区分开来。这些研究表明，甘油氧化为甲醛需要过氧化氢和非血红素铁。起作用的氧化剂不是超氧化物、过氧化氢或羟基自由基。细胞色素P450可能起到生成过氧化氢并还原非血红素铁的作用。由于微粒体生成甲醛的速率超过模型化学系统中的速率，P450可能还有其他作用。某些细胞色素P450同工酶，如P450 IIE1，过氧化氢生成速率的提高可能有助于提高甘油氧化的速率。
