title: Comparison of Posttranslational Modification and the Functional Impairment of Human Serum Albumin in Commercial Preparations.
abstract: On account of its long circulating half-life, human serum albumin (HSA) is susceptible to posttranslational modifications that can alter its functions. Here, we comprehensively compared the degree of posttranslational modifications with the functional impairment of HSA derived from 5 different commercially available albumin preparations and clarified their relationships. We used electrospray ionization-time of flight mass spectrometry to evaluate the degree of posttranslational modification of the entire HSA molecule that was associated with disease development and found that the fraction of Cys34-cysteinylated HSA (Cys-Cys34-HSA), a major form of oxidative modification, varied substantially among the albumin preparations. Meanwhile, no remarkable difference was found in the degree of glycated or N-terminal truncated HSA among the preparations tested. The nonosmotic pressure maintenance functions of HSA, such as its antioxidative and ligand-binding activities significantly differed among the preparations. Interestingly, the alternations of these functions showed a significantly negative correlation only with the Cys-Cys34-HSA fraction. These findings suggest that the Cys-Cys34-HSA fraction, as estimated by electrospray ionization-time of flight mass spectrometry can be used as a predictive marker for the functional impairment of albumin preparations and that it would be preferable to use albumin preparations with higher contents of functionally effective albumin that correspond to a lower degree of cysteinylation of Cys34 in clinical practice.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Miyamura
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Imafuku
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan; DDS Research Institute, Sojo University, Kumamoto 860-0082, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Anraku
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan; DDS Research Institute, Sojo University, Kumamoto 860-0082, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamasaki
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Tominaga
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ishima
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan; DDS Research Institute, Sojo University, Kumamoto 860-0082, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan. Electronic address: tomaru@gpo.kumamoto-u.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D015415:Biomarkers / Q000097:blood; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D015415:Biomarkers; D004364:Pharmaceutical Preparations; D012709:Serum Albumin; D003545:Cysteine
keywords: ESI-TOFMS; albumin preparation; antioxidative activity; cysteine 34; cysteinylation; ligand binding