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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
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 ?
Linkadge
Posted by linkadge on June 19, 2006, at 19:19:44
In reply to N methylated B carbolines...anyone ?, posted by linkadge on June 19, 2006, at 19:07:14
Consider these two seemingly contradictory studies.
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Human monoamine oxidase enzyme inhibition by coffee and beta-carbolines norharman and harman isolated from coffee.
Herraiz T, Chaparro C
Spanish Council for Scientific Research. CSIC. Instituto de Fermentaciones Industriales, Juan de la Cierva, 3, 28006 Madrid, Spain.
Monoamine oxidase (MAO) is a mitochondrial outer-membrane flavoenzyme involved in brain and peripheral oxidative catabolism of neurotransmitters and xenobiotic amines, including neurotoxic amines, and a well-known target for antidepressant and neuroprotective drugs. Recent epidemiological studies have consistently shown that coffee drinkers have an apparently lower incidence of Parkinson's disease (PD), suggesting that coffee might somehow act as a purported neuroprotectant. In this paper, "ready to drink" coffee brews exhibited inhibitory properties on recombinant human MAO A and B isozymes catalyzing the oxidative deamination of kynuramine, suggesting that coffee contains compounds acting as MAO inhibitors. MAO inhibition was reversible and competitive for MAO A and MAO B. Subsequently, the pyrido-indole (beta-carboline) alkaloids, norharman and harman, were identified and isolated from MAO-inhibiting coffee, and were good inhibitors on MAO A (harman and norharman) and MAO B (norharman) isozymes. beta-carbolines isolated from ready-to-drink coffee were competitive and reversible inhibitors and appeared up to 210 mug/L, confirming that coffee is the most important exogenous source of these alkaloids in addition to cigarette smoking. Inhibition of MAO enzymes by coffee and the presence of MAO inhibitors that are also neuroactive, such as beta-carbolines and eventually others, might play a role in the neuroactive actions including a purported neuroprotection associated with coffee consumption.
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On the other Hand
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Parkinson's disease (PD) is an aging-related movement disorder caused by a deficiency of the neurotransmitter dopamine (DA) in the striatum of the brain as a result of selective degeneration of nigrostriatal DA neurons. The molecular basis of the cell death of DA neurons is unknown, but one hypothesis is the presence of some amine-related neurotoxins that kill specifically nigrostriatal DA neurons over a long period of time. This neurotoxin hypothesis of PD started in the 1980s when 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was discovered to produce acutely PD-like symptoms. Two groups of natural MPTP-like and amine-related neurotoxins have been investigated as endogenous candidate compounds: isoquinolines (IQs) and beta-carbolines. These neurotoxins are speculated to cause oxidative stress, mitochondrial dysfunction, apoptotic cell death, and PD symptoms. However, since PD is a neurodegenerative disorder that progresses slowly over a period of many years, a long-term study may be required to elucidate the neurotoxicity of such neurotoxins in relation to PD.
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Linkadge
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
Posted by linkadge on June 20, 2006, at 17:34:15
In reply to Re: N methylated B carbolines...anyone ? » linkadge, posted by Larry Hoover on June 20, 2006, at 15:57:31
I suppose my question comes down to:
I am wondering if coffee and chocolate contain the type of beta carboline that has been linked in that study to dopaminegic neurotoxicity.
Linkadge
Posted by Larry Hoover on June 20, 2006, at 23:17:53
In reply to Re: N methylated B carbolines...anyone ?, posted by linkadge on June 20, 2006, at 17:34:15
> I suppose my question comes down to:
>
> I am wondering if coffee and chocolate contain the type of beta carboline that has been linked in that study to dopaminegic neurotoxicity.
>
> LinkadgeI am unaware of any toxic effects of alkaloids commonly found in coffee or chocolate, so I would let that be my guide. These two herbal products are known as neuroprotective agents, overall. Both contain dozens of alkaloids, which could include some that are adverse in effect, if taken in pure form. But the blend, the natural blend, does seem to be neuroprotective, for both coffee and chocolate. The benefits are thought to far outweight any risks. I don't even know of any risks, save from general over-consumption. Chocolate intoxication can be quite scary, for some people, I'm told. The Mayans used to induce it on purpose. It all depends on what you're looking for, eh?
Lar
Posted by llrrrpp on June 23, 2006, at 20:49:57
In reply to Re: N methylated B carbolines...anyone ? » linkadge, posted by Larry Hoover on June 20, 2006, at 23:17:53
Chocolate intoxication?!?
I have never experienced this, to my knowledge. I must be doing something wrong.
resonance structures... I remember this stuff. yeah!
Chemistry. what fun. and chocolate too.
sorry linkadge, I have nothing of substance to add. I have never noticed any harmful effects of chocolate. I'm going to have some right now, in fact 70% cocoa solids, with cocoa nibs, the little crunchies. oh yeah.
yours,
-ll
Posted by linkadge on June 25, 2006, at 14:46:45
In reply to Re: N methylated B carbolines...anyone ?, posted by llrrrpp on June 23, 2006, at 20:49:57
It was just this recent discovery that seemed to scare me. I suppose it was just assumed that the beta carbolines were neuroprotective. I suppose more studies are needed to confirm or reject what was proposed.
Linkadge
Posted by linkadge on July 2, 2006, at 20:44:21
In reply to Re: N methylated B carbolines...anyone ?, posted by llrrrpp on June 23, 2006, at 20:49:57
This is the end of the thread.
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