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Non-P450 oxidative metabolism: characteristics and drug substrates

Published on January 30, 2019   45 min

A selection of talks on Pharmaceutical Sciences

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0:00
Hello. My name is Dr. Christine Beedham, and I'm an honorary visiting senior lecturer at the University of Bradford. I'm going to talk about the Non-P450 enzymes which catalyze drug oxidation.
0:14
Although oxidated metabolism is generally linked with the microsomal cytochrome P450 system, oxidative reactions are not restricted to cytochrome P450 or confined to the endoplasmic reticulum. Cytosolic and mitochondrial enzymes usually with complimentary substrate specificities to P450, also contribute to drug a metabolite oxidation. These enzymes include the molybdoflavoproteins or molybdenum hydroxylases, aldehyde oxidase and xanthine oxidase, NAD dependent aldehyde dehydrogenase and NAD dependent alcohol dehydrogenase, and the flavoprotein monoamine oxidase. These enzymes provide a very effective protection against xenobiotics, as they catalyze the rapid oxidation of numerous nitrogen-containing hetrocycles, aldehydes, alcohols, and amines. Which is either independent of cellular co-factors or dependent on ubiquitous NAD+ . Likewise, microsomal oxidation is not catalyzed exclusively by cytochrome P450. Reactive nucleophiles undergo N and S oxidation by the NADPH dependent flavin monooxygenases in liver and extra hepatic tissue.
1:33
This lecture will summarize the reactions catalyzed by these enzymes, consider their substrate specificities and factors affecting their activity, and thus their relative importance in the metabolism of drugs and xenobiotics.

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Non-P450 oxidative metabolism: characteristics and drug substrates

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