title: Spectroscopic Studies on the Molecular Ageing of Serum Albumin.
abstract: Pathological states in the organism, e.g., renal or hepatic diseases, cataract, dysfunction of coronary artery, diabetes mellitus, and also intensive workout, induce the structural modification of proteins called molecular ageing or N-A isomerization. The aim of this study was to analyze the structural changes of serum albumin caused by alkaline ageing using absorption, spectrofluorescence, and circular dichroism spectroscopy. The N-A isomerization generates significant changes in bovine (BSA) and human (HSA) serum albumin subdomains-the greatest changes were observed close to the tryptophanyl (Trp) and tyrosyl (Tyr) residue regions while a smaller change was observed in phenyloalanine (Phe) environment. Moreover, the changes in the polarity of the Trp neighborhood as well as the impact of the ageing process on α-helix, β-sheet content, and albumin molecule rotation degree have been analyzed. Based on the spectrofluorescence study, the alterations in metoprolol binding affinity to the specific sites that increase the toxicity of the drug were investigated.
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Chair and Department of Physical Pharmacy, Jagiellońska 4, 41-200 Sosnowiec, Poland. mchudzik@sum.edu.pl.
authors.forename: Mariola
authors.initials: M
authors.lastname: Chudzik
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Chair and Department of Physical Pharmacy, Jagiellońska 4, 41-200 Sosnowiec, Poland. mmaciazek@sum.edu.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Maciążek-Jurczyk
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Chair and Department of Physical Pharmacy, Jagiellońska 4, 41-200 Sosnowiec, Poland. bpawelczak@sum.edu.pl.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pawełczak
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Chair and Department of Physical Pharmacy, Jagiellońska 4, 41-200 Sosnowiec, Poland. asulkowska@sum.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Sułkowska
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D003198:Computer Simulation; D006801:Humans; D008790:Metoprolol / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry* / Q000648:ultrastructure*; D013050:Spectrometry, Fluorescence
chemical_list: D012709:Serum Albumin; D008790:Metoprolol
keywords: circular dichroism; metoprolol; molecular ageing; second derivative; serum albumin