UDP-glucuronosyltransferases

Published on June 30, 2024   53 min

A selection of talks on Biochemistry

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0:00
Welcome. My name is Abby Collier and this lecture is about UDP glucuronosyltransferases and they are an enzyme set that I will be referring to as UGTs throughout the talk.
0:14
The learning objectives for this lecture are to understand the role of glucuronidation which is the reaction performed by the UGTs in the metabolism of endogenous compounds in the body as well as antibiotics which are compounds from outside of the human body. We want you to learn about the co-substrates of UGTs and their reactions and where they take place in the cell and in the human body and understand the complexity of the UGT enzyme family. This includes learning probe substrates as well as bilirubin metabolism in the human body so that you understand genetic diseases and syndromes associated with these enzymes and their roles in adverse drug reactions.
0:57
This picture shows the phases of what we call xenobiotic metabolism and an example is using the drug phenytoin. From the top of the slide you can see phenytoin undergoing a Phase I metabolism reaction which is primarily reduction and oxidation and then from the metabolite 4-hydroxphenytoin through a Phase II metabolism reaction performed by the UGTs to a glucurinide. On the right hand side in orange, you can see how phenytoin goes from a very lipophilic drug to a slightly water soluble metabolite to a highly water soluble metabolite through Phase II and this enables excretion.
1:39
The Phase II biotransformation enzymes also called conjugating enzymes are transferases that primarily detoxify the human body. They are also found in other animals insects and plants. The reaction products performed with conjugation are far more soluble and are usually excreted by kidneys in the urine or sometimes in the bile. These Phase II enzymes are what we call bi-substrate enzymes. They work on the molecule of interest. But they also use a secondary molecule to transfer motese from. The enzyme reaction is to transfer a component of the co-substrate or all of it to the substrate and second from the bottom, you'll see an example of phenyl plus UDPGA, which is the co factor or the bi-substrate for the UGT enzyme becoming phenyl glucurinide plus UDP. Although many phase two enzymes work on metabolites as shown in the previous slide, they can also work directly on the drug chemical or compound of interest.

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