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Phase II metabolism

Published on October 1, 2007 Reviewed on April 12, 2022   36 min

A selection of talks on Genetics & Epigenetics

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0:00
Hello. I'm Ann Daly. For the next 40 minutes or so, I'm going to talk to you about phase II metabolism.
0:10
In this talk, I will start by considering general aspects of each phase II reaction, including issues such as the biochemical properties of each enzyme and some typical drug substrates. I will then go on to consider pharmacogenetic aspects of selected phase II reactions. Those that are most important in my view. Phase II metabolism involves the conjugation of drugs
0:37
and other related compounds with groups such as glucuronic acid and sulfate. This usually makes these compounds more soluble and easy to excrete. Many compounds undergo phase I metabolism prior to phase II, but this is not always the case. Phase II metabolism is usually detoxicating, but there are some exceptions to this.
1:08
This slide summarises the main conjugation reactions involved in human drug and xenobiotic metabolism. Some endogenous compounds are also metabolised by these reactions. Conjugation with glucuronic acid is carried out by the UDP-glucuronosyltransferases and can occur at hydroxyl, carboxyl, amino and sulfhydryl groups. Sulfate conjugation or sulfation is carried out by sulfotransferases and occurs at amino and hydroxyl groups. Methyl group conjugation occurs at hydroxyl, amino and sulfhydryl groups and is performed by methyltransferases. Acetyltransferases conjugate amino and hydroxyl groups with acetyl groups. Amino acid conjugation involves more than one enzyme and results in the conjugation of carboxyl groups with amino acids such as glycine. Finally, glutathione S-transferases conjugate electrophilic compounds containing groups such as epoxide and organic halides with glutathione.

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