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Printable Handouts
Navigable Slide Index
- Introduction
- Lecture outline
- Cytochrome P450s, drugs and diseases
- Human P450s, ca. 1985
- Human P450s classification
- Quantitation of P450s in human liver
- The enzymes of drug metabolism and P451
- Human enzymes in activation of carcinogens
- Human P450 enzymes and carcinogen activation
- The human P450 Family 1
- Sites of expression of family 1 P450s (mRNA)
- 1A1 & 1B1 expression in human lung (protein) (1)
- 1A1 & 1B1 expression in human lung (protein) (2)
- P450 1B1 in mitochondria and ER
- Aryl hydrocarbon hydroxylase (AHH) activity
- CYP1B1 induced mitochondrial dysfunction
- Rabbit P450 1A2
- P450s 1A1, 1A2, 1B1 X-ray crystal structures
- Docking of two pyrene molecules in P450 1A2
- Working model: Rabbit P450 1A2 & small ligands
- Active site cavity topology comparison
- Alpha-naphthoflavone
- Substrate binding cavities of P450s 1B1 and 1A2
- The upper corners of substrate binding cavity
- Alternative drug metabolism pathways
- DNA damage detection assay
- Activation of carcinogens by P450 1A2
- Human P450 and carcinogen activation
- Carcinogens activated by human P450 1B1
- Activation of benzo[a]pyrene by P450 (1A1/1B1)
- Carcinogens activation by P450 family 1 enzymes
- P450 studies & cancers
- P450 1A2 and caffeine
- 7-ethoxyresorufin O-deethylation and B[a]P7,8-diol
- Trimodal distribution of AHH activity
- 17-beta estradiol hydroxylation by P450 systems
- Selective inhibition of P450 family 1 enzymes
- Issues regarding family 1 induction
- Heterocyclic arylamines (HAAs)
- A problem in P450 species extrapolation (1)
- A problem in P450 species extrapolation (2)
- Genotoxicity in some human samples
- Human P450 1A2 allelic variants (coding region)
- Immunoblot analysis of P450 1A2 expression
- Mutagenicity assay with MeIQ
- Kinetic parameters for P450 1A2 allelic variants
- Variations in the family 1 P450s: catalytic activity
- Summary
- Acknowledgements
Topics Covered
- Family 1 P450
- Substrates
- Regulation
- Polymorphisms
- Levels of activity and cancer
- Adverse drug reactions
- P450 systems and drug development
- Molecular epidemiology in cancer issues
Links
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Therapeutic Areas:
Talk Citation
Guengerich, F.P. (2016, July 31). Cytochrome P450 1 family: the roles of 1A1, 1A2 and 1B1 in drug metabolism [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 27, 2024, from https://doi.org/10.69645/GVWT4423.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. F. Peter Guengerich has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Cytochrome P450 1 family: the roles of 1A1, 1A2 and 1B1 in drug metabolism
A selection of talks on Biochemistry
Transcript
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0:00
FRED GUENGERICH: Hello, my
name is Dr. Fred Guengerich.
I'm at Vanderbilt University in
Nashville, Tennessee in the United States.
And today I'd like to
talk to you about cytochrome P450,
specifically the cytochrome P450
1 family and the roles of cytochromes
P450 1A1, 1A2, and
1B1 in the metabolism
of drugs and other things.
0:28
So what I'd like to do today
is talk about first of all
some background on cytochrome P450.
Most of my slides will use
the abbreviation, P450.
Some may use the CYP, which is
an acronym for cytochrome P450.
And I also talk about the
relevance to human health.
I am going to give you some
background on the P450 family 1
and some important concepts
from the literature;
particularly in
terms of localization
and the three-dimensional
structures of these enzymes
and their relevance to a function.
I'm going to talk
about more research
on these particular
P450s, the roles of family 1
P450s in the metabolism
of carcinogens.
I'll talk about induction and
inhibition, the significance
of genetic variations,
and also a little bit
about heterocyclic amines and
the possible risk from cancer.
1:30
So let's talk generally
about cytochrome P450s
and drugs and diseases.
In the human genome, we know
that there are exactly 57
cytochrome P450 genes and proteins.
Most of these are involved
in the metabolism of steroids
and other endogenous compounds,
but 15 of these at least
are involved in the
metabolism of drugs
and other xenobiotic chemicals.
Xenobiotic is a term
that we use to describe
compounds, chemicals that is,
that are not normally in the body.
For instance, drugs,
pesticides, things like this
would be in this regard.
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