Effect of protein-bound uraemic toxins on the thermodynamic characteristics of human albumin.
The ability of albumin to bind drugs and other lipophilic organic acids is decreased in chronic renal failure by the accumulation of albumin-bound uraemic toxins such as hippuric acid, indoxyl sulphate and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF). This furan acid is the most highly bound and is not removed by haemodialysis. The inhibitory effects of these three uraemic toxins on the interaction of three marker ligands sodium octanoate (for medium chain fatty acids), salicylic acid and phenol red (bilirubin site/site I) with albumin have been investigated by differential scanning microcalorimetry and flow microcalorimetry. CMPF was the most potent inhibitor and its binding site coincided with that of bilirubin (site I). Indoxyl sulphate binds to the site for medium-chain fatty acids and tryptophan (site II) and hippuric acid, the weakest inhibitor, inhibited binding to the salicylic acid site.
Sarnatskaya
Veronika V
VV
Section of Artificial Organs, Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, The National Academy of Sciences, 45 Vasilkovskaya Street, Kiev 03022, Ukraine.
Lindup
W Edward
WE
Niwa
Toshimitsu
T
Ivanov
Andrey I
AI
Yushko
Larisa A
LA
Tjia
John
J
Maslenny
Vitaly N
VN
Korneeva
Ludmila N
LN
Nikolaev
Vladimir G
VG
D000418:Albumins / Q000737:chemistry* / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D006626:Hippurates / Q000494:pharmacology*; D006801:Humans; D007200:Indican / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D013816:Thermodynamics
D000418:Albumins; D005663:Furans; D006626:Hippurates; D011422:Propionates; C041693:3-carboxy-4-methyl-5-propyl-2-furanpropionic acid; D007200:Indican; C030514:hippuric acid