Gemma Harris, Michelle L. Bradshaw, David J. Halsall, David J. Scott, Robert J. Unwin, Anthony G. W. Norden
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引用次数: 0
摘要
人们认为血浆中的大多数白蛋白都是单体,只有 5%的白蛋白是共价二聚体。然而,最近的生物物理学文献中有许多报告发现,白蛋白是可逆二聚化甚至寡聚化的。我们回顾了来自 X 射线晶体学和各种生物物理技术的相关数据。白蛋白的数均分子量会因二聚化而增加,从而影响白蛋白的大小依赖性过滤过程,如毛细血管内皮的糖萼和肾小球的荚膜细胞狭缝-隔膜。如果正确的话,根据 Kd 等过程的特点,血浆中白蛋白的可逆二聚化将对正常生理和医学产生重大影响。我们提出了二聚化对白蛋白分子形式和白蛋白平均分子量影响的定量模型,并估算了二聚化对白蛋白胶体渗透压的影响。二聚化会降低胶体渗透压,因为白蛋白的总浓度会增加到低于没有二聚化时的预期浓度。目前肾小球过滤白蛋白的模型需要修改,以考虑过滤白蛋白分子的动态大小。我们需要更可靠的生物物理数据来明确回答所提出的问题,并就此提出可行的方法。
Is there reversible dimerization of albumin in blood plasma? And does it matter?
Most albumin in blood plasma is thought to be monomeric with some 5% covalently dimerized. However, many reports in the recent biophysics literature find that albumin is reversibly dimerized or even oligomerized. We review data on this from X-ray crystallography and diverse biophysical techniques. The number-average molecular weight of albumin would be increased by dimerization, affecting size-dependent filtration processes of albumin such as at the glycocalyx of the capillary endothelium and the podocyte slit-diaphragm of the renal glomerulus. If correct, and depending on characteristics of the process, such as Kd, reversible dimerization of albumin in plasma would have major implications for normal physiology and medicine. We present quantitative models of the impact of dimerization on albumin molecular forms, on the number-average molecular weight of albumin, and estimate the effect on the colloid osmotic pressure of albumin. Dimerization reduces colloid osmotic pressure as total albumin concentration increases below that expected in the absence of dimerization. Current models of albumin filtration by the renal glomerulus would need revision to account for the dynamic size of albumin molecules filtered. More robust biophysical data are needed to give a definitive answer to the questions posed and we suggest possible approaches to this.
期刊介绍:
Experimental Physiology publishes research papers that report novel insights into homeostatic and adaptive responses in health, as well as those that further our understanding of pathophysiological mechanisms in disease. We encourage papers that embrace the journal’s orientation of translation and integration, including studies of the adaptive responses to exercise, acute and chronic environmental stressors, growth and aging, and diseases where integrative homeostatic mechanisms play a key role in the response to and evolution of the disease process. Examples of such diseases include hypertension, heart failure, hypoxic lung disease, endocrine and neurological disorders. We are also keen to publish research that has a translational aspect or clinical application. Comparative physiology work that can be applied to aid the understanding human physiology is also encouraged.
Manuscripts that report the use of bioinformatic, genomic, molecular, proteomic and cellular techniques to provide novel insights into integrative physiological and pathophysiological mechanisms are welcomed.