IUBio

[Protein-analysis] Re: http://en.wikipedia.org/wiki/Prion

Dr Engelbert Buxbaum engelbert_buxbaum at hotmail.com
Thu Aug 3 08:00:17 EST 2006


Being Riptup wrote:

> Dr Engelbert Buxbaum wrote:
> > Being Riptup wrote:
> >
> > > PrPC is found on the membranes
> > > of cells, though its normal function has not been fully resolved. Since
> > > the original hypothesis was proposed, a gene for PrP has been isolated:
> > > the Prnp gene.[8]
> >
> > One might add here that PrP-knock out mice have been generated and seem
> > normal in every respect, except that they are not susceptible to
> > spongiforme encephalopathy.
> 
> A prevalent genetic appendix? One found in mice, Elk, and felines.
> If you don't mind my saying so, I think that conclusion is hard to
> support, implying as it does that every test ever performed (and a
> great many that haven't been) on mice has been performed on prion-free
> mice.

Well, these knock-out mice live and breed normally.

> 
> What little I know of PrP, that it seems to be copper activated,
> sujests to me that it might be involved in inflammation. Some time ago,
> my mother's nursing textbook told me that Aspirin affected copper
> metabolism and probably works by doing so.

Aspirin (Bayer trade name for acetyl salicylate) works by chemically
modifying and inactivating an enzyme required for the synthesis of
prostaglandins, which are mediators of inflammation and pain.

> when the copper is oxidized.

Cu in the body occurs as Cu(II), Cu(I) compounds tend to be water to
insoluble and are easily oxidised to Cu(II), so they do not occur in
appreciable amounts in our body. Oxidation to (III) is not possible.

> I also hav difficulty believing that
> DNA encodes anything but the sequence of amino acids, so even if
> someone found a mutation that was more prone to exhibit disease
> characteristics, it wouldn't be prevalent.

Mutations where the onset of disease occurs late (after the age of main
reproductive activity) need not be evolutionary detrimental.
Nevertheless, mutations leading to FFI or CJD are relatively rare. The
mechanism leading to Huntingtons disease (elongation of a poly-Glu
stretch in the protein huntingtin) is quite interesting.
 
> The surjikal instrument vector is too much of a case history for me. Of
> course,
> wiki can get to a size that would be expensive to print, so that
> doesn't mean the information won't fit into a deep article.

Well, the idea of iatrogenic transmission is certainly worrying and
deserves mentioning. In addition, I simply find this incredible
stability of PrPsc interesting, as it flies in the face of everything we
think we know about proteins.


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