title: A mechanistic study of sialic acid mutarotation: implications for mutarotase enzymes.
abstract: The mutarotation of N-acetylneuraminic acid (Neu5Ac) proceeds by four kinetically distinct pathways: (i) the acid-catalyzed reaction of neutral Neu5Ac; (ii) the spontaneous reaction of the carboxylic acid (the kinetically equivalent acid-catalyzed reaction on the anion being ruled out by the solvent deuterium kinetic isotope effect of 3.74 ± 0.68); (iii) a spontaneous, water-catalyzed, reaction of the anion; and (iv) a specific-base catalyzed reaction of the anion. The magnitude of the solvent kinetic isotope effect, k(H2O)/k(D2O) = 4.48 ± 0.74 is consistent with a ring-opening transition state in which a water molecule is deprotonating the anomeric hydroxyl group in concert with strengthening solvation of the ring oxygen atom. The mechanistic implications for Neu5Ac mutarotases are discussed.
authors.affiliation: Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, V5A 1S6, British Columbia, Canada.
authors.forename: Jefferson
authors.initials: J
authors.lastname: Chan
authors.forename: Gurtej
authors.initials: G
authors.lastname: Sandhu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bennet
mesh_terms: D002238:Carbohydrate Epimerases / Q000378:metabolism*; D008847:Micromonospora / Q000201:enzymology*; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D002238:Carbohydrate Epimerases; C019646:aldose 1-epimerase; D019158:N-Acetylneuraminic Acid