Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, UK.
Department of Anaesthetics, Bradford Royal Infirmary, Bradford, UK.
Exp Physiol. 2024 Oct;109(10):1663-1671. doi: 10.1113/EP092012. Epub 2024 Aug 23.
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 K, 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.
大多数血浆白蛋白被认为是单体的，其中约 5% 通过共价键二聚化。然而，最近生物物理学文献中的许多报告发现白蛋白可可逆地二聚化甚至寡聚化。我们回顾了来自 X 射线晶体学和各种生物物理技术的数据。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，如毛细血管内皮细胞的糖萼和肾小球的足细胞裂孔隔膜。如果正确的话，并且取决于该过程的特征，如 K 值，白蛋白在血浆中的可逆二聚化将对正常生理学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、白蛋白数均分子量的影响的定量模型，并估计了对白蛋白胶体渗透压的影响。当总白蛋白浓度低于没有二聚化时的预期值时，二聚化会降低胶体渗透压。需要对当前的肾小球白蛋白过滤模型进行修订，以考虑过滤的白蛋白分子的动态大小。需要更可靠的生物物理数据来对提出的问题给出明确的答案，我们建议了可能的方法。
