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A comparative study of the chemical reactivity of pyridoxamine, Ac-Phe-Lys and Ac-Cys with various glycating carbonyl compounds

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Abstract

Pyridoxamine (PM) has long been known to inhibit protein glycation via various mechanisms of action. One such mechanism involves the scavenging of carbonyl compounds with glycating ability. Despite the abundant literature on this topic, few quantitative kinetic studies on the processes involved have been reported. In this work, we conducted a comparative kinetic study under physiological pH and temperature conditions of the reactions of PM, Ac-Phe-Lys and Ac-Cys with various glycating carbonyl compounds (viz. aldehydes, α-oxoaldehydes and ketones). The microscopic formation rate constants for Schiff bases of PM and various carbonyl compounds, k 1, are of the same order of magnitude as those for the Schiff bases of Ac-Phe-Lys. However, because PM exhibits a higher proportion of reactive form at physiological pH, its observed second-order rate constant is ca. five times greater than that for Ac-Phe-Lys. That could explain PM ability to compete with amino residues in protein glycation. On the other hand, the observed formation rate constant for thiohemiacetals is four orders of magnitude greater than the formation constants for the Schiff bases of PM, which excludes PM as a competitive inhibitor of Cys residues in protein glycation.

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Acknowledgments

This work was made possible by a grant from the Spanish Government (DGICYT CTQ 2005-00250) and from the Balearic Government (PROGECIB-28A).

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Authors and Affiliations

  1. Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, Cra. Valldemossa km 7.5, 07122, Palma de Mallorca, Spain

    Miquel Adrover, Bartolomé Vilanova, Juan Frau, Francisco Muñoz & Josefa Donoso

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  1. Miquel Adrover
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  2. Bartolomé Vilanova
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  3. Juan Frau
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  4. Francisco Muñoz
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  5. Josefa Donoso
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Correspondence to Bartolomé Vilanova.

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Adrover, M., Vilanova, B., Frau, J. et al. A comparative study of the chemical reactivity of pyridoxamine, Ac-Phe-Lys and Ac-Cys with various glycating carbonyl compounds. Amino Acids 36, 437–448 (2009). https://doi.org/10.1007/s00726-008-0098-6

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