What is the chemical reaction between aspirin and the cellular
component it works on- with covalent bonds shown? I can't find it.

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Request for Question Clarification by pafalafa-ga on 28 Mar 2005 11:46 PST

Here's an article that reports on the relatively recent findings of
how aspirin and other NSAIDs work at the biochemical level:


http://chronicle.uchicago.edu/950817/aspirin.shtml


Is this the sort of information you're looking for?

pafalafa-ga

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Request for Question Clarification by markj-ga on 28 Mar 2005 16:30 PST

val1 --

Check out the last section of the attached document, the one labeled
"How Does Aspiring Work?".  Is that what you are looking for?

http://www.chem.missouri.edu/GatesGroup/ExamTwoKEY-2003.pdf


markj-ga

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Clarification of Question by val1-ga on 28 Mar 2005 17:30 PST

I am more interested in the actual chemical reaction, showing the
covalent bond between aspirin and the cellular component it works on.

With great respect to pafalafa, the article cited refers to work
performed nearly ten years ago, and much has changed, not  the least
being the names of the probable molecular target enzymes.  They are
now better known as COX-1 and COX-2.

Here is a more recent review:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14592543

Other mechanisms of action than COX-1/2 inhibition are suspected, and
among these, the modulation of NF-kappa-B through altering the
phosphorylation and degradation of I-kappa-B is considered
significant.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15036249

http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?form=6&db=t&Dopt=s&uid=27242

You may need to download and install the 3D viewer.

The last one was aspirin with Prostaglandin synthetase (which may not
be too useful).
This one is COX-2 with indomethacin (somewhat akin to aspirin).  It is
a quite messy structure, and you may need to fiddle with the view and
which parts of the model are displayed to see what is going on.
http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?form=6&db=t&Dopt=s&uid=6776

There doesn't seem to be a structure in the database for COX1/2 & aspirin.

I'm not sure that aspirin is an irreversible binder, that is,
covalently bound.  It may just depend on hydrogen bonding (and
similar) to hold it in place.  I'll see what I can find.

Apparently, aspirin acetylates COX-2:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12106797

Aspirin acetylates amino acid 530 of the cyclooxygenase enzymes, which
is serine, hence it is a standard acetylation of the -OH on the Ser
residue.

Oh, and to answer xarqi, arg 120 is the site of hydrogen bonding in
cox-1 and 2 for most non-selective cox inhibitors, so it is correct
that usually there is no covalent bonding. (That's why aspirin is such
a good drug for blood thinning, is that it permanently knocks out the
cox enzymes in platelets once it acetylates them, and platelets cannot
make new enzymes) (Also, cox-2 specific inhibitors covalently bind.)
And heck, as long as I'm on this topic, the main difference between
cox-1 and -2 is amino acid 523-- in cox-1 it's iso and in cox-2 it's
val (and also phe and leu 385 I think)! That's a small difference!