Degradation of beta-lactam antibiotics in the presence of Zn2+ and 2-amino-2-hydroxymethylpropane-1,3-diol (Tris). A hypothetical non-enzymic model of beta-lactamases.
The system composed of 2-amino-2-hydroxymethylpropane-1,3-diol (Tris) and Zn2+ catalyses the degradation of cephalosporins. The beta-lactam opening fits to a first-order process, with a constant directly proportional to the zinc ion concentration. The pH and Tris concentration dependency displayed by the first-order constant, as well as the nature of the degradation products point to a mechanism that can be considered as an extension of that proposed for the benzylpenicillin degradation. The mechanism proposed here, and the values of the kinetic constants calculated, as compared with those of beta-lactamases, lead to the conclusion that the Tris-Zn2+ system simulates the catalytic action of the serine beta-lactamases rather than the action of the Zn(2+)-dependent type of enzymes.
Company
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Departamento de Quimica Fisica Aplicada, Universidad Autónoma de Madrid, Spain.
Benitez
M J
MJ
Jiménez
J S
JS
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D002509:Cephaloridine / Q000737:chemistry; D007700:Kinetics; D008433:Mathematics; D008956:Models, Chemical; D008962:Models, Theoretical; D013329:Structure-Activity Relationship; D014325:Tromethamine; D015032:Zinc; D001618:beta-Lactamases / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D014325:Tromethamine; D001618:beta-Lactamases; D015032:Zinc; D002509:Cephaloridine