健康人的尿液中为什么会有蛋白质?

Why are there proteins in the urine of healthy people?

蛋白质是人必需的营养物质,但为什么会有一小部分蛋白质通过尿液被排掉?健康人尿液中的蛋白质含量较低,而其种类却十分丰富,其中存在的蛋白质可能是机体不需要的废弃物,也可能是会对机体产生毒害作用而必须被排出.相比小分子代谢物而言,蛋白质的结构复杂、功能多样,即使分子水平上的一个小的改变都会影响其后续的生物学功能,通过全面地比较血浆和尿液蛋白质组分子水平修饰上的差异,或许可为解释尿液中存在蛋白质的现象提供线索.在这项研究中,共收集了9例健康人的尿液和9例健康人的血浆样品,通过高分辨串联质谱及非标记定量的蛋白质组学技术对样本进行分析,并使用pFind非限制性修饰鉴定算法整体比较了两种类型样品之间的分子修饰差异情况.结果表明,尿液蛋白质组中的半胱氨酸(cysteine, Cys)修饰变为脱氢丙氨酸(dehydroalanine, Dha)的数量显著高于血浆.[Cys→Dha]这种分子修饰破坏了原有蛋白质的二硫键,从而影响甚至改变蛋白质的结构与生物功能.综上,本研究揭示了血浆和尿液在整体蛋白质组修饰上的差异,并指出可能由于蛋白质分子修饰的差异造成了其结构不可逆的改变,进而使得失去功能或者有毒的蛋白质经血液被排进尿液中.

Proteins are essential nutrients for humans, but why is there a small amount of proteins excreted through urine? Although healthy people have low levels of protein in the urine, they are rich in variety. The proteins in them may be unnecessary wastes of the body or may even have a toxic effect on the body and must be excreted. Compared with small-molecule metabolites, proteins have a complex structure and various functions. Even a small change at the molecular level will affect their subsequent biological functions. A comprehensive comparison of the molecular level modifications of plasma and urine proteome, the difference may provide clues to the presence of protein in the urine. In this study, a total of 9 healthy people’s urine and 9 healthy people’s plasma samples were collected. The samples were analyzed by high-resolution tandem mass spectrometry and unlabeled quantitative proteomics techniques, and the non-limiting modification identification algorithm was used to to compare molecular modifications between two types of samples as a whole. The results showed that the amount of cysteine(Cys) modification to dehydroalanine(Dha) in the urine proteome was higher than that in plasma. The molecular modification [Cys→Dha] destroys the disulfide bond of the original protein,thereby affecting or even changing the structure and biological function of the protein. Therefore, this study revealed the differences in the overall proteome modification of plasma and urine and pointed out that the structure of protein may be irreversibly changed due to the difference in modification of protein molecules, which in turn caused proteins which lost their functions and even toxic proteins from the blood to be excreted into the urine.