more P450 questions
"JWILSON 363-6806", 604
jwilson at IOS.BC.CA
Mon Sep 16 12:16:39 EST 1996
A few more comments on the P450 discussion:
The specificity problem with CYP enzymes depends on your intended use of them.
For biomonitoring, the catalytic activities offer a quick, easy way to
determine biological exposure to particular compounds (especially in the case
of CYP 1A1) and sometimes for determination of toxicity to the test organisms.
For the EROD assay, human or mammalian research may be a bit more complicated
in assessment due to the presence of CYP 1A2. However, in the case of
non-mammalian systems such as fish, CYP 1A2 is not present (it is due to a gene
duplication event after the mammalian group was formed). Therefore, you can be
confident that your activity is due to CYP 1A1.
Considering the wide variety of substrates for the P450 enzymes, it is not
really any wonder that a "specific" substrate is difficult to find, especially
between enzymes that are closely related. For some research this proves
difficult, but for field work, the catalytic activities can be very useful in
spite of this problem.
Institute of Ocean Sciences
Sidney, BC CANADA
>Hi Tox Fans,
>While we're on the subject........
>I have recently had cause to start reading the P450 literature in a
>critical manner. In many experiments the metabolism of a "specific"
>substrate is used to assess the presence and activity of a particular P450
>isoprotein. For instance, I have read papers stating that
>ethoyresorufin-O-deethylase (EROD) activity is specifically measuring
>CYP1A1 activity, while other investigators indicate CYP1A2 is also capable
>of metabolizing this substrate. Is or isn't ethoxyresorufin a "specific"
>substrate for CYP1A1? Is there a "specific" substrate that can discriminate
>CYP1A1 from 1A2 activity?
>Perhaps the problem is that a more careful or better defined use of the
>word "specific" is needed, in that it implies that (as in this example
>above) all P450s (and other enzymatic activities as well) except the
>"specific one" have no activity against the substrate in question. This is
>the definition I have in mind when someone tells me they are using a
>"specific substrate" to assess a "specific" enzymatic activity. Is this a
>resonable/logical definition for "specificity" ?
>Best of results,
>Dr. Charles A. Miller
>Dept. Environmental Health Sciences, SL29
>Room 374, Center for Bioenvironmental Research
>Tulane Univ. School of Public Health and Tropical Medicine
>1430 Tulane Ave.
>New Orleans, LA 70112
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