Classical monoamine oxidases and copper-containing semicarbazide-sensitive amine oxidases are drug targets for a variety of established and novel pharmaceuticals used to treat conditions such as depression, Parkinsonism and inflammatory disorders. Development of enzyme inhibitors, both historically and currently, assumes an underlying adherence of these enzymes to Michaelis-Menten kinetic principles. In this mini-review, we discuss historical data from several laboratories and novel data from our own laboratories which show clearly that such an assumption is invalid. Rather, these enzymes often display hormetic behaviour towards their substrates, resulting in bell-shaped kinetic plots. We outline possible underlying mechanisms which might account for this behaviour and show how novel reversible hormetic drugs may capitalise on these mechanisms to introduce a new dimension in selectivity. The potential future benefits for therapeutic modulation of amine oxidase activities are discussed.

A ON THE HORMETIC BEHAVIOUR OF DRUG BINDING TO DIFFERENT REDOX STATES OF AMINE OXIDASES ENZYMES.

DI PAOLO, MARIA LUISA;
2008

Abstract

Classical monoamine oxidases and copper-containing semicarbazide-sensitive amine oxidases are drug targets for a variety of established and novel pharmaceuticals used to treat conditions such as depression, Parkinsonism and inflammatory disorders. Development of enzyme inhibitors, both historically and currently, assumes an underlying adherence of these enzymes to Michaelis-Menten kinetic principles. In this mini-review, we discuss historical data from several laboratories and novel data from our own laboratories which show clearly that such an assumption is invalid. Rather, these enzymes often display hormetic behaviour towards their substrates, resulting in bell-shaped kinetic plots. We outline possible underlying mechanisms which might account for this behaviour and show how novel reversible hormetic drugs may capitalise on these mechanisms to introduce a new dimension in selectivity. The potential future benefits for therapeutic modulation of amine oxidase activities are discussed.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2274601
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 1
  • ???jsp.display-item.citation.isi??? ND
  • OpenAlex ND
social impact