Effects of Heme Site (FA1) Ligands Bilirubin, Biliverdin, Hemin, and Methyl Orange on the Albumin Binding of Site I Marker Warfarin: Complex Allosteric Interactions

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F22%3A10455333" target="_blank" >RIV/00216208:11160/22:10455333 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rpvkNapIQP" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rpvkNapIQP</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms232214007" target="_blank" >10.3390/ijms232214007</a>

Result language

angličtina

Original language name

Effects of Heme Site (FA1) Ligands Bilirubin, Biliverdin, Hemin, and Methyl Orange on the Albumin Binding of Site I Marker Warfarin: Complex Allosteric Interactions

Original language description

Human serum albumin (HSA) is the most abundant plasma protein in circulation. The three most important drug-binding sites on HSA are Sudlow&apos;s Site I (subdomain IIA), Sudlow&apos;s Site II (subdomain IIIA), and Heme site (subdomain IB). Heme site and Site I are allosterically coupled; therefore, their ligands may be able to allosterically modulate the binding affinity of each other. In this study, the effects of four Heme site ligands (bilirubin, biliverdin, hemin, and methyl orange) on the interaction of the Site I ligand warfarin with HSA were tested, employing fluorescence spectroscopic, ultrafiltration, and ultracentrifugation studies. Our major results/conclusions are the following. (1) Quenching studies indicated no relevant interaction, while the other fluorescent model used suggested that each Heme site ligand strongly decreases the albumin binding of warfarin. (2) Ultrafiltration and ultracentrifugation studies demonstrated the complex modulation of warfarin-HSA interaction by the different Heme site markers; for example, bilirubin strongly decreased while methyl orange considerably increased the bound fraction of warfarin. (3) Fluorescence spectroscopic studies showed misleading results in these diligand-albumin interactions. (4) Different Heme site ligands can increase or decrease the albumin binding of warfarin and the outcome can even be concentration dependent (e.g., biliverdin and hemin).

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Molecular Sciences

ISSN

1422-0067

e-ISSN

—

Volume of the periodical

23

Issue of the periodical within the volume

22

Country of publishing house

CH - SWITZERLAND

Number of pages

18

Pages from-to

14007

UT code for WoS article

000888122200001

EID of the result in the Scopus database

2-s2.0-85142643194