Inactivation of glutathione reductase by 4-hydroxynonenal and other endogenous aldehydes.
Inactivation of glutathione reductase by 4-hydroxynonenal and other endogenous aldehydes.
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4-羟基壬烯醛和其他内源醛使谷胱甘肽还原酶失活。
DOI：
10.1016/s0006-2952(97)00090-7
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发表时间：
1997
影响因子：
5.8
通讯作者：
Royer,RE
中科院分区：
文献类型：
--
作者：
VanderJagt,DL;Hunsaker,LA;VanderJagt,TJ;Gomez,MS;Gonzales,DM;Deck,LM;Royer,RE
4-Hydroxynonenal 是不饱和脂质氧化降解的产物，是一种内源性反应性 α,β-不饱和醛，具有多种生物活性。 4-Hydroxynonenal 在 NADPH 依赖性反应中快速灭活谷胱甘肽还原酶。失活似乎涉及酶-失活剂复合物的初始形成，KD= 0.5 μM，随后发生失活反应，k = 1.3 × 10−2min.−1。 α,β-不饱和醛，如丙烯醛、巴豆醛和肉桂醛，也会使谷胱甘肽还原酶失活，但速率差异很大。 α,β-不饱和醛使谷胱甘肽还原酶失活，随后发生较慢的不依赖于 NADPH 的反应，导致形成非荧光交联产物，并伴有赖氨酸和组氨酸残基的损失。其他反应性内源醛，例如甲基乙二醛、3-脱氧葡萄糖醛和木糖酮，通过不依赖于 NADPH 的机制使谷胱甘肽还原酶失活，其中甲基乙二醛反应性最强。然而，2-氧代醛的效果远低于 4-羟基壬烯醛。这些 2-氧醛使谷胱甘肽还原酶失活，随后发生较慢的反应，导致在几周内形成荧光交联产物。这些变化伴随着精氨酸残基的损失。因此，与 2-氧醛相比，α,β-不饱和醛对谷胱甘肽还原酶的失活和修饰的事件顺序在动力学、NADPH 需求、荧光变化和氨基酸残基损失方面有所不同。低浓度的 4-羟基壬烯醛能够使谷胱甘肽还原酶（一种中心抗氧化酶）失活，这表明不饱和脂质的氧化降解可能会启动正反馈循环，从而增强氧化损伤的可能性。
4-Hydroxynonenal, a product of oxidative degradation of unsaturated lipids, is an endogenous reactive α,β-unsaturated aldehyde with numerous biological activities. 4-Hydroxynonenal rapidly inactivated glutathione reductase in an NADPH-dependent reaction. Inactivation appears to involve the initial formation of an enzyme-inactivator complex, KD= 0.5 μM, followed by the inactivation reaction, k = 1.3 × 10−2min.−1. α,β-Unsaturated aldehydes such as acrolein, crotonaldehyde, and cinnamaldehyde also inactivated glutathione reductase, although rates varied widely. Inactivation of glutathione reductase by α,β-unsaturated aldehydes was followed by slower NADPH-independent reactions that led to formation of nonfluorescent cross-linked products, accompanied by loss of lysine and histidine residues. Other reactive endogenous aldehydes such as methylglyoxal, 3-deoxyglucosone, and xylosone inactivated glutathione reductase by an NADPH-independent mechanism, with methylglyoxal being the most reactive. However, 2-oxoaldehydes were much less effective than 4-hydroxynonenal. Inactivation of glutathione reductase by these 2-oxoaldehydes was followed by slower reactions that led to the formation of fluorescent cross-linked products over a period of several weeks. These changes were accompanied by loss of arginine residues. Thus, the sequence of events is different for inactivation and modification of glutathione reductase by α,β-unsaturated aldehydes compared with 2-oxoaldehydes with respect to kinetics, NADPH requirements, fluorescence changes, and loss of amino acid residues. The ability of 4-hydroxynonenal at low concentrations to inactivate glutathione reductase, a central antioxidant enzyme, suggests that oxidative degradation of unsaturated lipids may initiate a positive feedback loop that enhances the potential for oxidative damage.