Type
ArticleKAUST Department
Smart Health Initiative (SHI) and Red Sea Research Center (RSRC), Bioscience Program, Biological and Environmental Science Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi ArabiaBioscience Program
Biological and Environmental Science and Engineering (BESE) Division
Red Sea Research Center (RSRC)
KAUST Grant Number
OSR-CRG2018-3792OSR-CRG2019-4088
Date
2022-07-11Permanent link to this record
http://hdl.handle.net/10754/679992
Metadata
Show full item recordAbstract
Human serum albumin (HSA) is the main zinc(II) carrier in blood plasma. The HSA site with the strongest affinity for zinc(II), multi-metal binding site A, is disrupted by the presence of fatty acids (FAs). Therefore, the FA concentration in the blood influences zinc distribution, which may affect both normal physiological processes and a range of diseases. Based on the current knowledge of HSA's structure and its coordination chemistry with zinc(II), we investigated zinc interactions and the effect of various FAs, including lipoic acid (LA), on the protein structure, stability, and zinc(II) binding. We combined NMR experiments and isothermal titration calorimetry to examine zinc(II) binding to HSA at a sub-atomic level in a quantitative manner as well as the effect of FAs. Free HSA results indicate the existence of one high-affinity zinc(II) binding site and multiple low-affinity sites. Upon the binding of FAs to HSA, we observed a range of behaviors in terms of zinc(II) affinity, depending on the type of FA. With FAs that disrupt zinc binding, the addition of LA restores HSA's affinity for zinc ions to the levels seen with free defatted HSA, indicating the possible mechanism of LA, which is effective in the treatment of diabetes and cardiovascular diseases.Citation
Al-Harthi, S., Chandra, K., & Jaremko, Ł. (2022). Lipoic Acid Restores Binding of Zinc Ions to Human Serum Albumin. Frontiers in Chemistry, 10. https://doi.org/10.3389/fchem.2022.942585Sponsors
This publication is based upon work supported by the King Abdullah University of Science and Technology (KAUST) Office of Sponsored Research (OSR) under Award No. OSR-CRG2018-3792 and Award No. OSR-CRG2019-4088 (LJ). Authors would like to thank Mariusz Jaremko, PhD, for helpful discussions at the early stages of the project.Publisher
Frontiers Media SAJournal
Frontiers in chemistryPubMed ID
35898971Additional Links
https://www.frontiersin.org/articles/10.3389/fchem.2022.942585/fullae974a485f413a2113503eed53cd6c53
10.3389/fchem.2022.942585
Scopus Count
Except where otherwise noted, this item's license is described as Archived with thanks to Frontiers in chemistry under a Creative Commons license, details at: https://creativecommons.org/licenses/by/4.0/
Related articles
- Towards the functional high-resolution coordination chemistry of blood plasma human serum albumin.
- Authors: Al-Harthi S, Lachowicz JI, Nowakowski ME, Jaremko M, Jaremko Ł
- Issue date: 2019 Sep
- Effect of Cu(2+) and Zn(2+) ions on human serum albumin interaction with plasma unsaturated fatty acids.
- Authors: Nemashkalova EL, Permyakov EA, Uversky VN, Permyakov SE, Litus EA
- Issue date: 2019 Jun 15
- The Influence of Fatty Acids on Metoprolol - Human Serum Albumin Interaction in Low Affinity Binding Sites: A Multifactorial NMR Approach.
- Authors: Szkudlarek A, Mogielnicki M, Pentak D, Ploch A, Maciazek-Jurczyk M
- Issue date: 2018
- Modulation of linoleic acid-binding properties of human serum albumin by divalent metal cations.
- Authors: Nemashkalova EL, Permyakov EA, Permyakov SE, Litus EA
- Issue date: 2017 Jun
- Allosteric modulation of zinc speciation by fatty acids.
- Authors: Barnett JP, Blindauer CA, Kassaar O, Khazaipoul S, Martin EM, Sadler PJ, Stewart AJ
- Issue date: 2013 Dec