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pH-Dependent Protein Binding Properties of Uremic Toxins In Vitro.
- Source :
-
Toxins [Toxins (Basel)] 2021 Feb 04; Vol. 13 (2). Date of Electronic Publication: 2021 Feb 04. - Publication Year :
- 2021
-
Abstract
- Protein-bound uremic toxins (PBUTs) are difficult to remove using conventional dialysis treatment owing to their high protein-binding affinity. As pH changes the conformation of proteins, it may be associated with the binding of uremic toxins. Albumin conformation at pH 2 to 13 was analyzed using circular dichroism. The protein binding behavior between indoxyl sulfate (IS) and albumin was examined using isothermal titration calorimetry. Albumin with IS, and serum with IS, p-cresyl sulfate, indole acetic acid or phenyl sulfate, as well as serum from hemodialysis patients, were adjusted pH of 3 to 11, and the concentration of the free PBUTs was measured using mass spectrometry. Albumin was unfolded at pH < 4 or >12, and weakened interaction with IS occurred at pH < 5 or >10. The concentration of free IS in the albumin solution was increased at pH 4.0 and pH 11.0. Addition of human serum to each toxin resulted in increased free forms at acidic and alkaline pH. The pH values of serums from patients undergoing hemodialysis adjusted to 3.4 and 11.3 resulted in increased concentrations of the free forms of PBUTs. In conclusion, acidic and alkaline pH conditions changed the albumin conformation and weakened the protein binding property of PBUTs in vitro.
- Subjects :
- Calorimetry
Circular Dichroism
Cresols blood
Humans
Hydrogen-Ion Concentration
Indican blood
Indoleacetic Acids blood
Protein Binding
Protein Conformation
Renal Dialysis
Renal Insufficiency, Chronic diagnosis
Renal Insufficiency, Chronic therapy
Serum Albumin, Human chemistry
Sulfuric Acid Esters blood
Uremia diagnosis
Uremia therapy
Renal Insufficiency, Chronic blood
Serum Albumin, Human metabolism
Toxins, Biological blood
Toxins, Biological metabolism
Uremia blood
Subjects
Details
- Language :
- English
- ISSN :
- 2072-6651
- Volume :
- 13
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxins
- Publication Type :
- Academic Journal
- Accession number :
- 33557434
- Full Text :
- https://doi.org/10.3390/toxins13020116