Guest guest Posted May 3, 2005 Report Share Posted May 3, 2005 Jim, Here are the papers: http://www.ub.rug.nl/eldoc/dis/medicine/e.j.van.der.wouden/c8.pdf http://tinyurl.com/62tz2 And if those dont work, here is Matts earlier post #92, from which I got both papers: infections/messag e/92 Your idea about the metro-wall could be right, but I cant really say. I dont know if the reduced (active) form circulates - I kinda suspect not - in the 2nd paper there they found that non-metro- reducing cells were unharmed when mixed with metro and metro- reducing cells. The reduced form may be so reactive that it exists only something very roughly like one second or less, before being re- oxidized in a reaction that damages some other molecule. Also, enzymes are not depleted or worn out by use; they are just molecular machines that basically stay in good shape, re-usably. Saturation occurs if there is too much substrate present, relative to the number of copies of the enzyme - the enzymes get " backed up " , at which point the enzymatic reaction does not stop, but its rate has maxed out and substrate may continue to accumulate. But some enzymes in the liver (and elsewhere?) are inducible, meaning the body can sense their saturation and respond by synthesizing extra enzyme copies. All my knowledge is pretty vague since I'm just taking early college bio classes now. I think I see what you mean about what Wheldon's saying. By non- replicating form, do you know if he means the elementary body, or something else? > Re: Metranidazole > > > Message: 25 > Date: Tue, 03 May 2005 17:13:58 -0000 > From: " Hodologica " <usenethod@y...> > Subject: Re: Metranidazole > , thanks for your warm welcome! > > - your comments made for what is either a > brilliant flash, or a brain-fart, depending.... Your > underlining of what the reference said, that > metronidazole has to be reduced by enzymes within the > cell before it is in active form, made me wonder > whether the " metro wall " comes about when we have used > up all the enzymes available and now the unreduced > form (which could be more toxic) is building up. Since > I don't know the whole pathway and what enzymes are > used within the cell, and whether the liver handles > the reduced form of metro differently than the > unreduced, it's hard to know. > > Any thoughts out there about this? Those who tolerate > metro for longer courses may just have more of that > enzyme or it's constituents available, or be able to > produce it better in their own cells. > > One difference in how I read Wheldon: he isn't saying > that " doxy and azithromycin cause Cpn to become > metro-sensitive or more metro-sensitive, " he (and > Stratton) are saying that these abx inhibit and kill > it in the replicating phase of the organism and some > of it adapts by shifting into the cryptic, > nonreplicating phase where it is still metabolizing > energy from body cells, but not replicating-- so it is > safe from abx but not safe from an intracellular agent > like metro. > > Also- your first link didn't work, do you have another > source for it? > Thanks, > Jim ===================================== > Metronidazole in itself is inactive... it becomes > active when reduced > by certain enzymes, as Jims ref says. This is almost > certainly what is > meant by the statement that a bacterium needs to > express certain > gene(s) - genes encoding such enzyme(s) - in order to > be sensitive to > metronidazole. > > I wouldnt know whether any bacterium can be > unequivocally stated to > lack any genes suitable for reducing metronidazole at > an appreciable > rate. I was under the very vague impression that all > bacterial taxa > had many genes whose products and functions are yet > unknown, but that > could be totally wrong - and perhaps there is a way to > prove, without > knowing its function positiviely, that a certain gene > does not code a > reducing enzyme. I wouldnt know. > > This paper, posted by Matt when he discussed metro, > suggests that > under some circumstances multiple classes of enzymes > may be able to > contribute to reduction of metro, at least in a some > amount > (Discussion, paragraph 2). One would have to do some > quantitative > reckoning to decide whether these phenomena might be > theraputically > relevant. > > http://jb.asm.org/cgi/content/full/182/18/50 > > Finally, I think to decide whether Bb can be sensitive > to metro one > really needs to examine the Brorsons empirical work on > the subject, > and herxoid experiences described by patients. > > SOmething also of interest in this question would be > Wheldons > assertion (I think) that doxy and azithromycin cause > Cpn to become > metro-sensitive or more metro-sensitive. > > Also, another factor re metro in general is that the > presence of much > oxygen may reconvert the reduced, active metro back > into inactive > from, spontaneously, without enzymatic action - I cant > remember where > I read that, or if I totally made it up - anyway heres > the other paper > Matt posted, which addresses some of this chemistry: > > http://www.ub.rug.nl/eldoc/dis/medicine/e.j.van.der.wouden/c8.pdf Quote Link to comment Share on other sites More sharing options...
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