title: Pyridoxal 5'-phosphate: electrophilic catalyst extraordinaire.
abstract: Studies of nonenzymatic electrophilic catalysis of carbon deprotonation of glycine show that pyridoxal 5'-phosphate (PLP) strongly enhances the carbon acidity of alpha-amino acids, but that this is not the overriding mechanistic imperative for cofactor catalysis. Although the fully protonated PLP-glycine iminium ion adduct exhibits an extraordinary low alpha-imino carbon acidity (pK(a)=6), the more weakly acidic zwitterionic iminium ion adduct (pK(a)=17) is selected for use in enzymatic reactions. The similar alpha-imino carbon acidities of the iminium ion adducts of glycine with 5'-deoxypyridoxal and with phenylglyoxylate show that the cofactor pyridine nitrogen plays a relatively minor role in carbanion stabilization. The 5'-phosphodianion group of PLP likely plays an important role in catalysis by providing up to 12 kcal/mol of binding energy that may be utilized for transition state stabilization.
authors.affiliation: Department of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260-3000, USA. jrichard@buffalo.edu
authors.forename: John P
authors.initials: JP
authors.lastname: Richard
authors.forename: Tina L
authors.initials: TL
authors.lastname: Amyes
authors.forename: Juan
authors.initials: J
authors.lastname: Crugeiras
authors.forename: Ana
authors.initials: A
authors.lastname: Rios
mesh_terms: D000818:Animals; D055162:Biocatalysis; D006801:Humans; D015394:Molecular Structure; D011732:Pyridoxal Phosphate / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D011732:Pyridoxal Phosphate