Is there reversible dimerization of albumin in blood plasma? And does it matter?

Harris, Gemma; Bradshaw, Michelle L.; Halsall, David J.; Scott, David J.; Unwin, Robert J.; Norden, Anthony G. W.

Abstract

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.

Citation

Harris, G., Bradshaw, M. L., Halsall, D. J., Scott, D. J., Unwin, R. J., & Norden, A. G. W. (2024). Is there reversible dimerization of albumin in blood plasma? And does it matter?. Experimental Physiology, 109(10), 1663-1671. https://doi.org/10.1113/EP092012

• Journal Article Type: Article
• Acceptance Date: Jul 26, 2024
• Online Publication Date: Aug 23, 2024
• Publication Date: Oct 1, 2024
• Deposit Date: Oct 12, 2024
• Publicly Available Date: Oct 15, 2024
• Journal: Experimental Physiology
• Print ISSN: 0958-0670
• Electronic ISSN: 1469-445X
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 109
• Issue: 10
• Pages: 1663-1671
• DOI: https://doi.org/10.1113/EP092012
• Keywords: fatty‐acid‐free albumin, plasma colloid osmotic pressure, dimerization, albumin
• Public URL: https://nottingham-repository.worktribe.com/output/38898349
• Publisher URL: https://physoc.onlinelibrary.wiley.com/doi/10.1113/EP092012