Posted by Larry Hoover on June 20, 2006, at 15:57:31
In reply to N methylated B carbolines...anyone ?, posted by linkadge on June 19, 2006, at 19:07:14
> I have read some contradictory things. I have read that beta carbolines are neuroprotective, but then I read that "N methylated" Beta carbolines are highly neurotoxic, like MPTP (or something).
>
> Does anyone know the difference between beta carbolines and "N methylated" beta carbolines ?
>
> LinkadgeYes. ;-)
Well, it also matters which N is methylated, but I'll try and give you the most likely general case.
http://en.wikipedia.org/wiki/Beta-carboline
In the diagram, it is the N (nitrogen atom) to the right that is the active nitrogen. Apart from that right-hand ring, the beta-carbolines have all the rest of the structure just the same. Where it shows R1, that's an indication that Mama Nature has variations of the basic structure, where the nature of the R-functional group determines the specific chemical under consideration.
The nitrogen atom immediately adjacent to the R-group is a very special nitrogen atom. It has two bonds, rather than the normal (for nitrogen) three. Moreover, the ring it is a member of is a resonance structure, which stabilizes both of those bonds that it shares with the ring. What makes that nitrogen special, though, is that it has a lone pair of electrons, oriented directly out from the centre of the ring. Those electrons are highly repulsive to other electorns, and when the carboline binds to a receptor, it can push away sites of similar enhanced electron density, or pull towards it sites of lower electron density. In other words, the surface arrangement of electrons in this molecule can bend the physical conformation of other molecules. That's what happens to receptors, when their natural ligands bind to them.
Exogenous ligands, molecules from outside the body that nevertheless bind to a receptor, can agonize or antagonize the receptor they bind to. Or, they can inhibit an enzyme, just by binding to it. It wastes the enzyme's time, so to speak.
So, it does depend on where the carboline binds, just what it will do. You can't generalize with respect to good or bad, on the binding affinity alone.
If that special nitrogen atom I've been talking about is methylated, it no longer displays that lone pair of electrons. It's like a rubber cap pulled over it, insulating it from what it otherwise might have been able to accomplish. Methylation can be good. It can be bad. It depends.
Lar
poster:Larry Hoover
thread:658853
URL: http://www.dr-bob.org/babble/alter/20060601/msgs/659299.html