Reyftmann J P, Santus R, Mazière J C, Morlière P, Salmon S, Candide C, Mazière C, Haigle J
Laboratoire de Physico-Chimie de l'Adaptation Biologique, INSERM U 312, Muséum National d'Histoire Naturelle, Paris, France.
Biochim Biophys Acta. 1990 Feb 6;1042(2):159-67. doi: 10.1016/0005-2760(90)90002-f.
Tryptamine, serotonin and tryptophan are readily oxidized during the Cu2+-catalyzed peroxidation of arachidonic acid (AA) at neutral pH and under certain experimental conditions which determine their relative susceptibility to oxidation. Thus, in AA micelles, fluorescence spectroscopy demonstrates that positively-charged indoles interact with negatively-charged micelles while Trp remains in the aqueous phase. As a result, serotonin and tryptamine are preferentially oxidized. In egg phosphatidylcholine liposomes loaded with AA, the three substrates interact with vesicles and undergo lipid-induced oxidation. EDTA inhibits the formation of thiobarbituric-reactive substances (TBARS) and prevents the indoles from oxidation. Owing to the intricate contact between the lipidic core and the apolipoproteins, the Trp residues of human serum LDL and HDL3 are very rapidly oxidized, i.e., at least one order of magnitude faster than Tyr HDL and Lys LDL, which are believed to be involved in the binding of these lipoproteins to their cell receptors. Cupric ions are rather specific for the lipid-induced autoxidation of Trp residues of lipoproteins whereas in micelles and liposomes, Mn2+ and Fe2+ can lead to TBARS production and to oxidation of indoles. This specificity is surprising considering the known ability of Fe2+ to catalyze LDL modification (measured by TBARS production) during their incubation with various cells. Biological consequences of the easy lipid-induced oxidation of biologically important indoles are discussed.
在中性pH值以及某些决定其相对氧化敏感性的实验条件下，色胺、血清素和色氨酸在铜离子催化的花生四烯酸（AA）过氧化过程中很容易被氧化。因此，在AA胶束中，荧光光谱表明带正电荷的吲哚与带负电荷的胶束相互作用，而色氨酸仍留在水相中。结果，血清素和色胺优先被氧化。在装载有AA的鸡蛋磷脂酰胆碱脂质体中，这三种底物与囊泡相互作用并发生脂质诱导的氧化。乙二胺四乙酸（EDTA）抑制硫代巴比妥酸反应性物质（TBARS）的形成，并防止吲哚被氧化。由于脂质核心与载脂蛋白之间存在复杂的接触，人血清低密度脂蛋白（LDL）和高密度脂蛋白3（HDL3）中的色氨酸残基被非常迅速地氧化，即至少比据信参与这些脂蛋白与其细胞受体结合的高密度脂蛋白中的酪氨酸（Tyr HDL）和低密度脂蛋白中的赖氨酸（Lys LDL）快一个数量级。铜离子对脂蛋白色氨酸残基的脂质诱导自氧化具有相当的特异性，而在胶束和脂质体中，锰离子（Mn2+）和亚铁离子（Fe2+）可导致TBARS的产生和吲哚的氧化。考虑到亚铁离子在与各种细胞孵育期间催化低密度脂蛋白修饰（通过TBARS产生来衡量）的已知能力，这种特异性令人惊讶。文中讨论了生物重要吲哚容易发生脂质诱导氧化的生物学后果。
