Received: by alpheratz.cpm.aca.mmu.ac.uk id LAA10080 (8.6.9/5.3[ref pg@gmsl.co.uk] for cpm.aca.mmu.ac.uk from fmb-majordomo@mmu.ac.uk); Sat, 2 Dec 2000 11:08:36 GMT Message-ID: <3A28D6C6.14D2AC51@icon.co.za> Date: Sat, 02 Dec 2000 13:02:30 +0200 From: A van Gelder <cardiac@icon.co.za> X-Mailer: Mozilla 4.73 [en] (Win98; U) X-Accept-Language: en To: memetics@mmu.ac.uk, Bruce Alan Johnson <baj.liberty@mindspring.com> Subject: Prions Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Sender: fmb-majordomo@mmu.ac.uk Precedence: bulk Reply-To: memetics@mmu.ac.uk
Scott Chase asked:
>
> As a molecular entity, the prion is quite bizarre. What exactly is it?
> What's its modus operandi?
>
I am no expert on prions but offer the following as what may be an
interesting aside for some. If there is further interest I will do some
reading and come up with a more complete picture unless an expert comes
up with a better explanation beforehand.
When I was a medical student a few decades ago we were taught virusses
were inanimate. Heck, you could even crystalyze "it"! At that time, the
main scientific mental model of a virus was still some "thing" existing
in a fluid that could be "filtered" through a membrane small enough to
stop all known bacteria some textbooks still referred to "filterable
virus" (singular), neatly coupled with electron micrographs of neat
little hexagons of viral "bodies" (never called "corpses" I seem to
recall.
Now we routinely "kill" virusses and we have in mind a quite complex
"organism" consisting of nucleic acid wearing a protein cloak, even
enzyme systems to help it along in its jumping act between bigger
organisms.
Now prions are "inanimate" (!) bits of protein that have the funny
property to interfere with the process of "folding" of protein
molecules. You see, the idea that the DNA sequence first translated into
RNA, selecting amino acids which are then assembled on ribosomes into
the sequence expressed by triads of nucleic acid subgroups has not been
sufficient to explain the very complex "folding" that the assembled
protein molecule undergoes during or soon after this assembly process.
And, it is the shape of the protein molecule that determines which bits
are attractive to bits of other protein molecules and where they then
stick together, or repulse another. (And you thought it was LOVE making
the world go round!)
Prions seem to either act as faulty templates for proteins to fold
against (also in the process incidently making more prions), or to
damage the endoplasmic reticulum where this protein-folding is taking
place. The end result is that the protein being synthesized has an
abnormal shape, if not amino-acid sequence, causing it to polymerize
into denser pieces. It is this abnormal protein that does not work and
cannot be broken down or ejected from the cells that leads to cell
damage and death (in neural cells) with the spongy areas of destruction
in the final condition.
As far as the indestructible properties of prions are concerned this is
likely to be very relative, sterilization procedures are designed to
kill bacteria (and viri) without destroying the material being
sterilized. Pasteurization is an extreme example where bacterial protein
components are destroyed by heat, without "cooking" the protein in the
milk. Cooked milk may be viewed foating on the surface in some coffee
shops.
Also, not all protein eaten is degraded to the level of amino acid or
polypeptide (a very short chain of amino acids) by intestinal enzymes.
Food allergy (eg hives after certain forms of sea food) is due to the
absorbtion by normal gut of fully fledged protein molecules. So there is
no need to postulate "special" routes or properties of "infection" by
prions. Absorbtion is likely to be related to the amount ingested which
is the basis for the UK recommendation to remove all contact between
neural tissue and the meat being sold, so removing the spinal cord
together with the enclosed bony spinal column from the human food chain.
Of course Creutzfeld Jacob disease has been said to be transferred
during the transplantation of human corneas.
The suggestion that a very small intake could lead to a small number of
molecules finding their way to the brain, and then just taking longer to
get to the point where sufficient damage is done to recognize the
disease is the basis for the concern of "long incubation Creutzfeld
Jacob Disease (CJD)as opposed to Juvenile CJD.
Of course, there is another school of thought that considers the
Juvenile Creutzfeld Jacob cases in the UK to be close to the natural
mutation rate of the genes influencing all this folding - - - -
Antoine van Gelder snr
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