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Printable Handouts
Navigable Slide Index
- Introduction
- Code for slides with supplementary information
- Arylamine N-acetyltransferases (NATs)
- The future from first edition of talk
- Talk overview
- Acetylation
- Reaction mechanism
- N-acetylation of isoniazid (INH)
- Hydralazine conversion to triazolophthalazine
- Cyclization helps create triazolophthalazine
- Pharmacogenetics (1)
- Isoniazid metabolism in Caucasian population
- Metabolism is by acetylation
- Genotype is related to acetylator phenotype
- Human chromosome 8p22 (NAT genes)
- Human NAT1 & NAT2: substrate specificity profile
- NAT1 and NAT2 alleles
- Amino acid substitutions in human NAT1 & NAT2
- Pharmacogenetics (2)
- Human NAT2
- Human NAT2 metabolises a range of drugs
- The human NAT2 gene
- Human NAT2: the 'slow' acetylator
- Pharmacogenetics: effect of ethnicity
- Human NAT enzyme alleles: ethnic distribution
- Sequence analysis of NAT1 & NAT2
- Global distribution of NAT2 acetylation phenotypes
- Extended NAT haplotypes
- NAT2 gene diversity
- Insulin resistance and 803A NAT2 mutation
- Amino acid substitutions in NAT1 & NAT2: K268R
- Pharmacogenetics: NAT1 and NAT2
- SNPs cause slow acetylation (structural studies)
- Understanding NAT protein structure
- 3D structure of NAT
- Selenomethionine labelling
- Active site of NAT
- Active site residues and N and C termini (1)
- Active site residues and N and C termini (2)
- Active site residues and N and C termini (3)
- Ball and stick model of NAT active site
- Substrate specificity of WT & F125S NAT1
- Substrate binding pockets of human NAT1 & NAT2
- SNPs cause slow acetylation (tissue expression)
- Amino acid substitutions in NAT1 & NAT2: R64W
- Slow acetylation & NAT protein expression in liver
- Murine NAT2 enzymic activity in liver
- Mutations cause NAT to cluster for degradation
- Ubiquitination of NAT1 proteins
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 1 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 23, 2024, from https://doi.org/10.69645/ASKO8371.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 1
A selection of talks on Biochemistry
Transcript
Please wait while the transcript is being prepared...
0:00
Arylamine N-acetyltransferases,
I'm Edith Sim.
I'm going to be talking about a family
of drug metabolizing enzymes.
And I have been working on this family of enzymes
for more than 20 years.
And this represents an update
on what was presented previously
in a former version of a Henry Stewart talk.
0:30
As a code, slides with an "S" in the upper left hand corner
contain advanced supplementary information
in addition to the core material which is presented
throughout the talk.
0:46
Arylamine N-acetyltransferases
are cytosolic enzymes
which are commonly called phase II drug metabolizing enzymes.
They're around 30-34 kDa in size,
and are widespread amongst eukaryotes and prokaryotes.
They were first recognized
for their role in the N-acetylation
of hydrazines and arylamines.
1:15
At the end of the first edition of the Henry Stewart talk,
I suggested that the future
would be the 3D structure of NAT from mammals,
and the effects of mutation on activity.
And I ask the question:
"Whether NAT has a rule in addition
to drug metabolizing enzymatic activity?"
In this talk, next, I'm going to identify to what extent the future is here.
And the answer is that
most of these future ideas will be covered
in the current talk.
The overview of the talk that I am going to give today is: