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- Introduction
-
1. Editor's foreword
- Prof. Ann Daly
-
2. Introduction to drug metabolism enzymes
- Dr. Dennis Smith
- General factors affecting drug metabolism
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3. General factors affecting drug metabolism: effect of physiological factors and disease 1
- Prof. Edward T. Morgan
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4. General factors affecting drug metabolism: effect of physiological factors and disease 2
- Prof. Edward T. Morgan
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5. Drug metabolism in liver disease
- Dr. Nathalie Zgheib
- Prof. Robert Branch
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7. Prediction of pathways of drug metabolism
- Dr. Maurice Dickins
- Phase I metabolizing enzymes: cytochrome P450s
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8. Cytochrome P450 1 family: the roles of 1A1, 1A2 and 1B1 in drug metabolism
- Prof. F. Peter Guengerich
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9. CYP2 family
- Prof. Ann Daly
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10. Why study the cytochrome P4503A (CYP3A) family?
- Dr. Erin Schuetz
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11. Pharmacogenomics: an update
- Prof. Magnus Ingelman-Sundberg
- Phase I metabolizing enzymes: non-cytochrome P450s
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12. Non-P450 oxidative metabolism: characteristics and drug substrates
- Dr. Christine Beedham
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13. UDP-glucuronosyltransferases
- Prof. Abby Collier
- Phase II metabolizing enzymes: conjugating enzymes
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14. Glutathione transferases
- Prof. Ralf Morgenstern
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15. Arylamine N-acetyltransferases 1
- Prof. Edith Sim
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16. Arylamine N-acetyltransferases 2
- Prof. Edith Sim
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17. Arylamine N-acetyltransferases 3
- Prof. Edith Sim
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18. Methyltransferases
- Prof. Richard Weinshilboum
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19. Amino acid conjugation: mechanism and enzymology
- Dr. Kathleen Knights
- Clinical aspects
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20. Clinical significance of enzyme induction and inhibition
- Prof. Kim Brøsen
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21. Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism
- Prof. Julia Stingl (formerly Kirchheiner)
- Latest Updates in the Field
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22. Mammalian flavin-containing monooxygenases
- Prof. Allan Rettie
- Archived Lectures *These may not cover the latest advances in the field
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23. Glucuronidation and the UDP - glucuronosyltransferases
- Prof. Peter Mackenzie
- Prof. John Miners
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25. Catalytic cycle of cytochrome P450s
- Prof. Gordon Roberts
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26. Drug metabolism and liver disease
- Prof. Robert Branch
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27. Crystal structures of drug-metabolizing P450 monooxygenases
- Prof. Eric Johnson
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28. Sulfation and human cytosolic sulfotransferases
- Prof. Charles Falany
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29. Laboratory methods for the in vitro study of drug metabolism
- Dr. Charles Crespi
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30. Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism: psychopharmacology and pain
- Prof. Julia Stingl (formerly Kirchheiner)
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32. Pharmacogenomics
- Prof. Magnus Ingelman-Sundberg
Printable Handouts
Navigable Slide Index
- Introduction
- Human NAT1
- Evolutionary tree of NATs in primates
- NAT1 expression in gut
- Human NAT1 expression during development
- Human NAT1 expression in placentae
- Human NAT2 expression in placentae
- Human NAT1 gene
- Analysis of human NAT1 & NAT2 genes
- NAT1: prognostic biomarker in male breast cancer
- NAT1 expression in breast tumours
- NAT1 activity in breast cancer cell lines
- Greater survival rate with NAT1 positive tumours
- Rapid screening: detecting substrates & inhibitors
- Mammalian NATs
- Rodent NAT2 resembles human NAT1
- Activity profile of mouse NAT2
- Human NAT1 and murine equivalent
- Mouse Nat genes
- Murine NAT2 (fast & slow strains)
- Murine NAT2 is the equivalent of human NAT1
- Effects of MNAT2 mutation F125S
- C-terminal comparison of HNAT1 & MNAT2
- NAT2 in murine developing neural tube (1)
- NAT2 in murine developing neural tube (2)
- Understanding endogenous function of an enzyme
- Does human NAT1 have an endogenous role?
- Mouse models
- Generation of a Nat2 knock-out mouse construct
- Nat2 gene is expressed widely in skin
- Nat knock-out mice are healthy
- Characterisation of Nat2 knock-out mice
- NAT expression during mouse development
- Nat knock-out & gene expression
- Excess "endogenous" NAT expression
- Chimeric mice overexpressing huNAT1
- Overexpression of human NAT1
- Pabaglu: possible endogenous substrate for NAT
- NAT, AcetylCoA and folate relationship
- HNAT1 & mouse homologue are AcCoA hydrolases
- Reaction mechanism & hydrolysis: role of folate
- MNAT2 as a folate-dependent AcCoA hydrolase
- MNAT2 AcCoA hydrolysis in the presence of folate
- AcCoA hydrolysis reaction: 2 possible mechanisms
- Human NAT1 C-terminus controls activity
- Arylamine presence affects ACoA hydrolysis
- C-terminus controls activity of aryl-NAT
- Acetyl CoA binding site
- CoA binding to human NAT2 vs. MMNAT
- Eukaryotic inter-domain loop & CoA
- AcCoA binding to human NAT1: role of lysine
- Structural similarity between folate and AcCoA
- Folate docking into the active site of (Human)NAT1
Topics Covered
- Mechanism of action
- Reaction substrates
- Isoform substrate profiles
- Isoenzymes NAT1 and NAT2
- Regulation of gene expression
- Pharmacogenetics
- Phenotype/genotype correlation
- Ethnic variation
- Transgenic mouse models
- NAT protein structures
- NAT as a biomarker in breast cancer
- NAT inhibitors as diagnostic agents
- NAT in mycobacteria
- NAT inhibitors as an approach to potential anti-tubercular agents
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Sim, E. (2016, July 28). Arylamine N-acetyltransferases 2 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved May 13, 2025, from https://doi.org/10.69645/LEGX9619.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Edith Sim has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Arylamine N-acetyltransferases 2
A selection of talks on Cardiovascular & Metabolic
Transcript
Please wait while the transcript is being prepared...
0:00
Arylamine
N-acetyltransferases. Part 2
I'm Edith Sim and I've been
working on these enzymes
for over 20 years.
0:11
So human NAT1 is a phase II
drug-metabolizing enzyme.
It's over 80% identical
to human NAT2.
It's widespread
tissue distribution.
It is also subject
to genetic polymorphism.
And the genetic polymorphism,
like in human NAT2,
appears in many instances
and result in the protein
being degraded within cells,
therefore, being unavailable
to carrier deacetylation.
Human NAT1 has got a different
substrate specificity
then human NAT2.
It N-acetylates,
para-aminobenzoic acid
and para-aminosalicylate.
It's expressed
early in development,
unlike human NAT2.
It is overexpressed
in ER positive breast cancer.
And recently it's also been
demonstrated that
it hydrolyses acetylCoA
in the presence of folate.
1:09
The evolution of a tree
of NATs in primates,
although all of these enzymes
are very similar,
clearly divides
into three groups.
The NAT1s, the NAT2s,
and the NAT pseudo genes.
Therefore, this suggests
that the duplication
of these loci occurred
prior to the break time
or the development
of the different strands
of the primate derivatives.