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As mentioned above, in certain cases the metabolites are so reactive that they do not escape the enzyme that formed them and covalently bind to the enzyme leading to irreversible inhibition.39 This is referred to as mechanism- based inactivation as metioned above, and in the case of P450 enzymes, it may result from irreversible alkylation of an active site amino acid or the heme prosthetic group or a combination of both alkylation of heme inactivates P450, whereas amino acid alkylation does not always result in loss of catalytic activity