Registration for a live webinar on 'Precision medicine treatment for anticancer drug resistance' is now open.
See webinar detailsWe noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
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 December 22, 2024, 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 Pharmaceutical Sciences
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.