CARNOSINE, HOMOCARNOSINE AND ANSERINE - COULD THEY ACT AS ANTIOXIDANTS INVIVO

CARNOSINE, HOMOCARNOSINE AND ANSERINE - COULD THEY ACT AS ANTIOXIDANTS INVIVO
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DOI:
10.1042/bj2640863
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发表时间:
1989-12-15
影响因子:
4.1
通讯作者:
HALLIWELL, B
HALLIWELL, B
中科院分区:
生物学3区
文献类型:
--
作者:
ARUOMA, OI;LAUGHTON, MJ;HALLIWELL, B

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肌肽、高肌肽和鹅肌肽已被提出作为体内抗氧化剂。我们的研究表明,这三种化合物都是很好的羟基自由基(.OH)的清除剂,但它们都不能与超氧自由基,过氧化氢或次氯酸在生物学上显着的速率反应。它们都不能以干扰脱氧核糖的“位点特异性”铁依赖性自由基损伤的方式结合铁离子,也不能限制Cu 2+对菲咯啉的可用性。高肌肽对铁离子依赖性脂质过氧化没有影响;肌肽和鹅肌肽在某些(但不是所有)测定系统中以高浓度使用时具有弱抑制作用。然而,这些化合物干扰硫代巴比妥酸(TBA)测试的常用版本的能力可能导致高估了它们在以前的一些研究中抑制脂质过氧化的能力。相比之下,组氨酸刺激铁离子依赖性脂质过氧化。它的结论是,由于在体内存在的高浓度,肌肽和鹅肌肽可以想象作为生理抗氧化剂清除。OH,但他们没有一个广泛的抗氧化活性,他们的能力,抑制脂质过氧化作用没有很好地建立。可能是它们具有除抗氧化保护以外的功能(例如缓冲),但它们比组氨酸更安全地积累,组氨酸对铁离子依赖性脂质过氧化具有显著的促氧化作用。鉴于这两种分子之间明显的结构相似性,高肌肽无法与HOCl反应、干扰TBA测试或以与肌肽相同的方式影响脂质过氧化系统,这是令人惊讶的。
Carnosine, homocarnosine and anserine have been proposed to act as antioxidants in vivo. Our studies show that all three compounds are good scavengers of the hydroxyl radical (.OH) but that none of them can react with superoxide radical, hydrogen peroxide or hypochlorous acid at biologically significant rates. None of them can bind iron ions in ways that interfere with ''site-specific'' iron-dependent radical damage to the sugar deoxyribose, nor can they restrict the availability of Cu2+ to phenanthroline. Homocarnosine has no effect on iron ion-dependent lipid peroxidation; carnosine and anserine have weak inhibitory effects when used at high concentrations in some (but not all) assay systems. However, the ability of these compounds to interfere with a commonly used version of the thiobarbituric acid (TBA) test may have led to an overestimate of their ability to inhibit lipid peroxidation in some previous studies. By contrast, histidine stimulated iron ion-dependent lipid peroxidation. It is concluded that, because of the high concentrations present in vivo, carnosine and anserine could conceivably act as physiological antioxidants by scavenging .OH, but that they do not have a broad spectrum of antioxidant activity, and their ability to inhibit lipid peroxidation is not well established. It may be that they have a function other than antioxidant protection (e.g. buffering), but that they are safer to accumulate than histidine, which has a marked pro-oxidant action upon iron ion-dependent lipid peroxidation. The inability of homocarnosine to react with HOCl, interfere with the TBA test or affect lipid peroxidation systems in the same way as carnosine is surprising in view of the apparent structural similarity between these two molecules.