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Mechanisms and consequences of carbamoylation
Nature Reviews Nephrology ( IF 28.6 ) Pub Date : 2017-07-31 , DOI: 10.1038/nrneph.2017.103
Sigurd Delanghe , Joris R. Delanghe , Reinhart Speeckaert , Wim Van Biesen , Marijn M. Speeckaert

Protein carbamoylation is a non-enzymatic post-translational modification that binds isocyanic acid, which can be derived from the dissociation of urea or from the myeloperoxidase-mediated catabolism of thiocyanate, to the free amino groups of a multitude of proteins. Although the term 'carbamoylation' is usually replaced by the term “carbamylation” in the literature, carbamylation refers to a different chemical reaction (the reversible interaction of CO2 with α and ε-amino groups of proteins). Depending on the altered molecule (for example, collagen, erythropoietin, haemoglobin, low-density lipoprotein or high-density lipoprotein), carbamoylation can have different pathophysiological effects. Carbamoylated proteins have been linked to atherosclerosis, lipid metabolism, immune system dysfunction (such as inhibition of the classical complement pathway, inhibition of complement-dependent rituximab cytotoxicity, reduced oxidative neutrophil burst, and the formation of anti-carbamoylated protein antibodies) and renal fibrosis. In this Review, we discuss the carbamoylation process and evaluate the available biomarkers of carbamoylation (for example, homocitrulline, the percentage of carbamoylated albumin, carbamoylated haemoglobin, and carbamoylated low-density lipoprotein). We also discuss the relationship between carbamoylation and the occurrence of cardiovascular events and mortality in patients with chronic kidney disease and assess the effects of strategies to lower the carbamoylation load.



中文翻译:

氨基甲酰化的机理和后果

蛋白质氨基甲酰化是一种非酶翻译后修饰,可将异氰酸与多种蛋白质的游离氨基结合,异氰酸可源自尿素的解离或髓过氧化物酶介导的硫氰酸酯分解代谢。尽管在文献中术语“氨基甲酸酯化”通常由术语“氨基甲酸酯化”代替,但氨基甲酸酯化是指不同的化学反应(CO 2的可逆相互作用带有蛋白质的α和ε-氨基)。根据所改变的分子(例如胶原蛋白,促红细胞生成素,血红蛋白,低密度脂蛋白或高密度脂蛋白),氨甲酰化作用可能具有不同的病理生理作用。氨基甲酸酯化的蛋白质与动脉粥样硬化,脂质代谢,免疫系统功能障碍(例如抑制经典补体途径,抑制补体依赖性利妥昔单抗的细胞毒性,氧化性中性粒细胞爆发减少以及抗氨基甲酰化蛋白质抗体的形成)有关。 。在本综述中,我们讨论了氨基甲酰化的过程并评估了氨基甲酰化的可用生物标志物(例如,高瓜氨酸,氨基甲酰化白蛋白的百分比,氨基甲酸酯化的血红蛋白和氨基甲酸酯化的低密度脂蛋白)。

更新日期:2017-09-06
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