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Postby bromley » Sat Apr 15, 2006 8:38 am

Glutamate has often been cited as being involved in the cascade of events in MS. The following research suggests that there might be a drug to help (I must admit I found the article difficult to decipher).

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Re: Glutamate

Postby NHE » Sat Apr 15, 2006 10:20 pm

Bromley wrote:I must admit I found the article difficult to decipher

I think I would file it under the "neuroprotection" category. They are using a drug to inhibit cell signaling cascades that are elicited by glutamate via the NMDA receptor. They're inhibitor acts via uncompetitive inhibition. While this might sound confusing at first, all it means that the drug binds to the NMDA receptor at a site other than the binding site for glutamate.

The term "uncompetitive inhibition" is carried over from enzyme kinetics since receptor binding kinetics is mathematically studied in the same way that enzyme kinetics are studied. For example, let's take the case of enzymes which have an active site where a substrate binds and undergoes chemical modification. If a drug binds to the active site and prevents the substrate from binding, then it's competitively inhibiting the enzyme. However, if a drug binds to some other site on the enzyme and causes some change in the enzyme, usually a change in the shape of the enzyme which perturbs the shape of the active site and prevents the chemical modification of the substrate, then the drug is said to act through uncompetitive inhibition. An uncompetitive inhibitor is distinguished by the fact that it only binds to the enzyme after the substrate has bound to the active site, i.e., it only binds to the enzyme substrate complex. This differs from a non-competitive inhibitor which acts in a similar fashion but can bind to either the enzyme alone or the enzyme substrate complex. So, with respect to the NMDA receptor antagonist used in the study it is binding to the receptor+glutamate complex and inhibiting the normal signaling cascades that usually occur as a result of glutamate thereby protecting the oligodendrocytes.

Anyways, it's been a while since I've had any biochemistry so I hope that the above explanation is clear enough.

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