Monosaccharide autoxidation in health and disease.
Monosaccharide autoxidation in health and disease.
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DOI：
10.1289/ehp.8564297
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发表时间：
1985-12
影响因子：
10.4
通讯作者：
Thornalley PJ
中科院分区：
文献类型：
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作者：
Thornalley PJ
简单单糖的烯-二醇互变异构体还原氧产生过氧化氢和α-氧代醛。这个过程，称为单糖自氧化，发生在生理pH值和温度，并可能有助于几个病理过程的发展。单糖烯醇化为烯-二醇互变异构体是单糖与氧反应的先决条件。反应动力学表明一个两步过程：单糖烯醇化为烯-二醇，然后烯-二醇与氧气反应。烯-二醇与氧反应形成自由基反应中间体：在生理条件下形成超氧化物、semidione和1-羟烷基自由基（在高pH值下也可检测到羟基自由基）。单糖的自氧化刺激红细胞中氧合血红蛋白的氧化，产生高铁血红蛋白和过氧化氢，以及还原的吡啶核苷酸NAD（P）H氧化为氧化的同系物NAD（P）+和无酶活性的核苷酸。这在体外刺激红细胞中的氧化代谢（通过己糖单磷酸分流）和α-乙醛代谢（通过谷胱甘肽酶系统）。即使使用非常高浓度（50 mM）的单糖，氧化挑战也相对温和。然而，通过α-氧代醛的膜蛋白的交联被增强;这种作用可能会加剧老化并减少循环中红细胞的寿命。在体内，单糖的自氧化预期是在生物组织中发生的慢性氧化过程，其利用简单的单糖，例如，糖酵解和糖异生。单糖自氧化被认为是控制细胞有丝分裂和衰老的决定因素，为谷胱甘肽酶系统提供生理底物，并可能导致与糖尿病和吸烟相关的慢性疾病过程。
The reduction of oxygen by the ene-diol tautomer of simple monosaccharides produces hydrogen peroxide and alpha-oxoaldehydes. This process, termed monosaccharide autoxidation, occurs at physiological pH and temperature and may contribute to the development of several pathological processes. Enolization of the monosaccharide to an ene-diol tautomer is a prerequisite for the reaction of the monosaccharides with oxygen. The reaction kinetics suggest a two step process: the enolization of the monosaccharide to the ene-diol followed by the reaction of the ene-diol with oxygen. Free-radical reactive intermediates are formed by the reaction of the ene-diol with oxygen: superoxide, semidione, and 1-hydroxyalkyl radicals are formed under physiological conditions (hydroxyl radicals are also detected at high pH). The autoxidation of monosaccharides stimulates the oxidation of oxyhemoglobin in erythrocytes, producing methemoglobin and hydrogen peroxide, and the oxidation of reduced pyridine nucleotides NAD(P)H to the oxidized congener NAD(P)+ and enzymatically inactive nucleotide. This stimulates oxidative metabolism (via the hexose monophosphate shunt) and alpha-oxoaldehyde metabolism (via the glyoxalase system) in erythrocytes in vitro. The oxidative challenge is relatively mild even with very high concentrations (50 mM) of monosaccharide. However, crosslinking of membrane proteins by alpha-oxoaldehydes is enhanced; this effect may exacerbate ageing and decrease the lifetime of erythrocytes in circulation. In vivo, the autoxidation of monosaccharides is expected to be a chronic oxidative process occurring in biological tissue which utilises simple monosaccharides, e.g., in glycolysis and gluconeogenesis. Monosaccharide autoxidation is suggested to be a determinant in the control of cellular mitosis and ageing, providing physiological substrates for the glyoxalase system, and may contribute to the chronic disease processes associated with diabetes mellitus and the smoking of tobacco.