Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications.
Detoxification of aldehydes by histidine-containing dipeptides: from chemistry to clinical implications.
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DOI：
10.1016/j.cbi.2012.12.017
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发表时间：
2013-02-25
影响因子：
5.1
通讯作者：
Barski, Oleg A.
中科院分区：
文献类型：
--
作者：
Xie, Zhengzhi;Baba, Shahid P.;Sweeney, Brooke R.;Barski, Oleg A.
在动脉粥样硬化、心肌和脑缺血、糖尿病、神经退行性疾病和创伤期间的代谢失衡和氧化应激条件下，氧化脂质和碳水化合物会产生大量的醛。在大多数组织中，醛通过氧化还原酶解毒，氧化还原酶催化醛的氧化或还原或与低分子量硫醇和胺（例如谷胱甘肽和组氨酸二肽）的酶促和非酶促缀合。组氨酸二肽以微摩尔至毫摩尔范围存在于脊椎动物的组织中，参与多种生理功能，例如pH缓冲、金属螯合、氧化剂和醛清除。组氨酸二肽如肌肽与脂质衍生的不饱和醛形成迈克尔加合物，并与碳水化合物衍生的氧代醛和羟基醛反应，形成未知结构的产物。尽管这些肽与亲电子分子的反应速率低于谷胱甘肽，但它们可以保护谷胱甘肽免受氧化剂修饰，并且它们对于谷胱甘肽耗尽的细胞或谷胱甘肽稀缺的细胞外空间中的醛猝灭可能很重要。与体外研究结果一致，肌肽治疗已被证明可以减少缺血性损伤，改善血糖控制，改善糖尿病和肥胖动物模型并发症的发生，促进伤口愈合并减少动脉粥样硬化。肌肽的保护作用与其抗氧化特性、促进糖酵解、解毒活性醛和提高组胺水平的能力有关。因此，用肌肽和相关的组氨酸二肽治疗可能是预防和治疗与高羰基负荷相关的疾病的有前途的策略。
Aldehydes are generated by oxidized lipids and carbohydrates at increased levels under conditions of metabolic imbalance and oxidative stress during atherosclerosis, myocardial and cerebral ischemia, diabetes, neurodegenerative diseases and trauma. In most tissues, aldehydes are detoxified by oxidoreductases that catalyze the oxidation or the reduction of aldehydes or enzymatic and nonenzymatic conjugation with low molecular weight thiols and amines, such as glutathione and histidine dipeptides. Histidine dipeptides are present in micromolar to millimolar range in the tissues of vertebrates, where they are involved in a variety of physiological functions such as pH buffering, metal chelation, oxidant and aldehyde scavenging. Histidine dipeptides such as carnosine form Michael adducts with lipid-derived unsaturated aldehydes, and react with carbohydrate-derived oxo- and hydroxy- aldehydes forming products of unknown structure. Although these peptides react with electrophilic molecules at lower rate than glutathione, they can protect glutathione from modification by oxidant and they may be important for aldehyde quenching in glutathione-depleted cells or extracellular space where glutathione is scarce. Consistent with in vitro findings, treatment with carnosine has been shown to diminish ischemic injury, improve glucose control, ameliorate the development of complications in animal models of diabetes and obesity, promote wound healing and decrease atherosclerosis. The protective effects of carnosine have been linked to its anti-oxidant properties, it ability to promote glycolysis, detoxify reactive aldehydes and enhance histamine levels. Thus, treatment with carnosine and related histidine dipeptides may be a promising strategy for the prevention and treatment of diseases associated with high carbonyl load.
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影响因子：
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作者：
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