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Printable Handouts
Navigable Slide Index
- Introduction
- Topics to be considered
- Phase II metabolism
- Conjugation reactions
- Glucuronidation
- Glucuronidation reactions (1)
- Glucuronidation reactions (2)
- Properties of UGTs
- Human UGT genes
- UGT1A gene complex
- Drug substrate specificity of main UGT isoforms
- Effects of glucuronidation
- Induction of UGT
- Elimination of glucuronidated compounds
- Sulfotransferases (1)
- Reaction catalysed by sulfotransferase
- Sulfotransferases (2)
- Amino acid conjugation
- Acetylation
- Properties of acetyltransferases
- NAT drug substrates
- Sulfanilamide acetylation
- Glutathione
- Glutathione S-Transferases (GST)
- Glutathione S-transferase reaction
- Drugs conjugated by GST
- Glutathione conjugate excretion
- Multiple forms of GST
- Induction of GST
- Methyltransferases
- Methyltransferase reactions
- Methyltransferase reactions - examples
- Phase II pharmacogenetics
- GST polymorphisms
- GSTM1 polymorphism
- GSTT1
- Ethnic variation in GSTT1 and M1 polymorphisms
- NAT2 polymorphism
- NAT2 - common variant alleles
- Ethnic variation in frequency of NAT2 polymorphism
- Polymorphism in UGT1A1
- Gilbert's syndrome: molecular basis
- UGT2B7 polymorphism
- TPMT polymorphism - population study
- TPMT polymorphism - molecular basis
- Catechol O-methyltransferase polymorphism
- Summary
- References
Topics Covered
- Phase II metabolism
- Conjugation of drugs and other xenobiotics with a range of different molecules including glucuronic acid, sulfate, amino acids, acetyl groups, methyl groups and glutathione
- Properties of the enzyme families catalyzing these conjugation reactions
- Typical drug-based examples of individual reactions
- Genes encoding Phase II enzymes
- Functionally significant polymorphisms and their effects
Links
Series:
Categories:
Talk Citation
Daly, A. (2022, April 12). Phase II metabolism [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 25, 2024, from https://doi.org/10.69645/AXRC2746.Export Citation (RIS)
Publication History
Financial Disclosures
- Professor Ann Daly has no commercial/financial relationships to disclose.
A selection of talks on Metabolism & Nutrition
Transcript
Please wait while the transcript is being prepared...
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.