過(guò)氧化氫在微摩爾水平即對(duì)細(xì)胞有毒性,。大量的酶都對(duì)過(guò)氧化氫十分敏感而失活,，但是這種損傷往往是可逆的
近日,，美國(guó)伊利諾伊大學(xué)厄巴納－香檳分校Adil Anjem 和James A. Imlay做了一項(xiàng)有意義的實(shí)驗(yàn)，驗(yàn)證了單核金屬酶與過(guò)氧化氫的直接關(guān)系,，并且闡明了在過(guò)氧化氫環(huán)境下單核金屬酶失活的機(jī)制,。實(shí)驗(yàn)表明，多種酶對(duì)過(guò)氧化氫十分敏感而失活,，但是這種損傷往往是可逆的,。因此，使用特殊的離子來(lái)偶聯(lián)酶蛋白也許可以躲避氧化劑的危害,。此項(xiàng)研究,，發(fā)表在3月12日美國(guó)《生物化學(xué)期刊》(JBC)上。
由于非氧化還原金屬酶在體內(nèi)通常都因帶有金屬離子而帶有電荷,，因此,，這項(xiàng)研究測(cè)試這些酶是否因此而成為氧化反應(yīng)的主要目標(biāo)。事實(shí)上,，實(shí)驗(yàn)中的三種單核酶樣品（包括肽去甲酰酶,、蘇氨酸脫氫酶和胞嘧啶脫氫酶）在體外以及在大腸桿菌體內(nèi)會(huì)被微摩爾級(jí)的過(guò)氧化氫所迅速破壞,。
前兩種酶使用了一種半胱氨酸殘基以協(xié)調(diào)催化性的金屬原子，該反應(yīng)的定量測(cè)定可以由Fenton反應(yīng)測(cè)定,。為了避免其它活性殘基的非可逆性損傷,，氧化型的半胱氨酸可以由細(xì)胞內(nèi)還原劑所修復(fù)?？墒?，長(zhǎng)期的暴露在過(guò)氧化氫環(huán)境中，這些酶也會(huì)逐漸失活,。
在過(guò)氧化氫的環(huán)境中,，大腸桿菌通過(guò)誘導(dǎo)MntH、Dps來(lái)保護(hù)這三種蛋白,。這些蛋白可以協(xié)調(diào)作用,，通過(guò)調(diào)節(jié)非氧化型錳來(lái)代替金屬離子。（生物谷Bioon.com ）
doi: 10.1074/jbc.M111.330365
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Mononuclear iron enzymes are primary targets of hydrogen peroxide stress
Adil Anjem and James A. Imlay..
This study tested whether non-redox metalloenzymes are commonly charged with iron in vivo and are primary targets of oxidative stress because of it. Indeed, three sample mononuclear enzymes--peptide deformylase, threonine dehydrogenase, and cytosine deaminase--were rapidly damaged by micromolar hydrogen peroxide in vitro and in live Escherichia coli.The first two enzymes use a cysteine residue to coordinate the catalytic metal atom; it was quantitatively oxidized by the radical that the Fenton reaction generated. Since oxidized cysteine can be repaired by cellular reductants, the effect was to avoid irreversible damage to other active-site residues. Nevertheless, protracted H2O2 exposure gradually inactivated these enzymes, consistent with the overoxidation of the cysteine residue to sulfinic or sulfonic forms. During H2O2 stress E. coli defended all three proteins by inducing MntH, a manganese importer, and Dps, an iron-sequestration protein. These proteins appeared to collaborate in replacing the iron atom with non-oxidizable manganese. The implication is that mononuclear metalloproteins are common targets of H2O2 and that both structural and metabolic arrangements exist to protect them
