title: Acetaldehyde-derived modifications on cytosolic human carbonic anhydrases.
abstract: Acetaldehyde can generate modifications in several proteins, such as carbonic anhydrase (CA) II. In this study, we extended in vitro investigations on acetaldehyde adduct formation by focusing on the other human cytosolic CA enzymes I, III, VII, and XIII. High-resolution mass spectrometric analysis indicated that acetaldehyde most efficiently formed covalent adducts with CA II and XIII. The binding of up to 19 acetaldehydes in CA II is probably attributable to the high number of lysine residues (n = 24) located mainly on the surface of the enzyme molecule. CA XIII formed more adducts (up to 25) than it contains lysine residues (n = 16) in its primary structure. Acetaldehyde treatment induced only minor changes in CA catalytic activity in most cases. The present study provides the first evidence that acetaldehyde can bind to several cytosolic CA isozymes. The functional consequences of such modifications will be further investigated in vivo by using animal models.
authors.affiliation: Institute of Biomedical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Bootorabi
authors.forename: Janne
authors.initials: J
authors.lastname: Jänis
authors.forename: Vesa P
authors.initials: VP
authors.lastname: Hytönen
authors.forename: Jarkko
authors.initials: J
authors.lastname: Valjakka
authors.forename: Marianne
authors.initials: M
authors.lastname: Kuuslahti
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Onni
authors.initials: O
authors.lastname: Niemelä
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
mesh_terms: D000079:Acetaldehyde / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D011994:Recombinant Proteins; D002256:Carbonic Anhydrases; D000079:Acetaldehyde