title: Chronic liver and renal diseases differently affect structure of human serum albumin.
abstract: Human serum albumin (HSA) binding with endogenous metabolites and drugs is substantially decreased in chronic renal and liver diseases. To test the hypothesis that the decreased binding ability is caused by conformational changes of the protein, we analyzed infrared and Raman spectra of HSA isolated from healthy donors and patients with chronic uremia and liver cirrhosis. Uremia did not affect the secondary structure of HSA but modified the environment of its Asp/Glu residues. Liver cirrhosis increased the amount of extended and beta-structures, modified the environment of Asp/Glu and Tyr side chains, and changed the configuration of disulfide bridges in albumin molecules. The conformational changes of "cirrhotic" albumin were not caused by reversibly bound ligands and resembled a partial unfolding of the protein induced by adsorption on the charcoal surface. The dramatic structural alterations of HSA in liver cirrhosis may be caused by its oxidative modification and might underlie the decreased binding ability and changed body distribution of albumin.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Whitehead Medical Building, Room 123, 615 Michael Street, Atlanta, GA 30322, USA. aiivano@emory.edu
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Ivanov
authors.forename: Elena A
authors.initials: EA
authors.lastname: Korolenko
authors.forename: Elena V
authors.initials: EV
authors.lastname: Korolik
authors.forename: Stanislav P
authors.initials: SP
authors.lastname: Firsov
authors.forename: Rostislav G
authors.initials: RG
authors.lastname: Zhbankov
authors.forename: Mariusz K
authors.initials: MK
authors.lastname: Marchewka
authors.forename: Henryk
authors.initials: H
authors.lastname: Ratajczak
mesh_terms: D002908:Chronic Disease; D006801:Humans; D007674:Kidney Diseases / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood*; D008107:Liver Diseases / Q000097:blood*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012016:Reference Values; D012709:Serum Albumin / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013059:Spectrum Analysis, Raman; D014511:Uremia / Q000097:blood*
chemical_list: D012709:Serum Albumin