Posted by Larry Hoover on October 31, 2004, at 9:02:53
In reply to Re: Bowel toxins,enzyme peptide conversion of aminos? » Larry Hoover, posted by raybakes on October 31, 2004, at 7:21:30
> Hi Lar - just looking at what enzymes are in the gut from some abstracts...
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> This one on sulphation..
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> Distribution of 2-naphthol sulphotransferaseI think we better clear up what it is we're talking about.
Unfortunately, the terminology in enzymology is both inconsistent and sometimes contradictory. It needs an overhaul, but that hasn't happened yet.
A sulphotransferase is the enzyme which conjugates, via sulphonation, some substrate. That targets it for excretion, while at the same time, blocking its metabolic activity.
The corollary deconjugating enzyme is a sulphonase.
Usually, but not always, the identifying prefix, combined with the suffix -ase, means that it breaks the substance down. Examples are protease, lipase, lactase. So, glucoronidase and sulphonase are the deconjugating enzymes.
When you see the suffix -transferase, it is generally assumed that the enzyme adds the prefix substance. An aminotransferase adds the amine functional group to some substrate, for example. The conceptual problem is that some other molecule lost an amine group simultaneously. A methylating enzyme is also simultaneously a demethylating one, eh?
Then you get exceptions such as cyclooxygenase. It takes a linear polyunsturated fatty acid, and makes a ring out of it by adding oxygen. However, the name might also suggest that it does the exact opposite.
I just want to make sure that you focus your attention on the deconjugating enzymes.
>
> and this one on extrahepatic cytochromes..
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> Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts.
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> Ding X, Kaminsky LS.
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> Wadsworth Center, New York State Department of Health, State University of New York, Albany, New York 12201, USA. xding@wadsworth.org
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> Cytochrome P450 (CYP) enzymes in extrahepatic tissues often play a dominant role in target tissue metabolic activation of xenobiotic compounds. They may also determine drug efficacy and influence the tissue burden of foreign chemicals or bioavailability of therapeutic agents. This review focuses on xenobiotic-metabolizing CYPs of the human respiratory and gastrointestinal tracts, including the lung, trachea, nasal respiratory and olfactory mucosa, esophagus, stomach, small intestine, and colon. Many CYPs are expressed in one or more of these organs, including CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2F1, CYP2J2, CYP2S1, CYP3A4, CYP3A5, and CYP4B1. Of particular interest are the preferential expression of certain CYPs in the respiratory tract and the regional differences in CYP expression profile in different parts of the gastrointestinal tract. Current research activities on the characterization of CYP expression, function, and regulation in these tissues, as well as future research needs, are discussed.I just want to say that most of the drug interactions that people get concerned about actually take place in the wall of the intestine....at least those which have immediate effect.
> Although not expressed as highly as in the liver, I still feel they are important in the proper functioning of the bowel - I have seen some references to cyp3a4 in the bowel protecting the bowel wall from bile acids.
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> RayIf you're concerned about that, then don't ever consume grapefruit, as the effect is mediated in the gut wall, blocking 3A4.
If you want to induce 3A4, then take some St. John's wort.
My central point, hitherto unexpressed, is that there is a lot more to "hepatic" enzymes than meets the eye. We're only just starting to understand the complexity of interactions. Rather than trying to affect a specific aspect of e.g. hepatic function, it makes more sense to promote hepatic health. Unless, of course, a specific disorder is being considered.
Lar
poster:Larry Hoover
thread:407758
URL: http://www.dr-bob.org/babble/alter/20041022/msgs/409494.html