Cysteine & Glutathione

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First email on this -

The email below this one here is an email a mother of a DS child sent to me, when she was asking me some questions regarding this subject and this first email here is my response -

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Hi Sharon,

Lots of good questions!! I asked several of these questions to some folks a few months ago! Sounds like you have a pretty good doctor who's willing to look at the articles & asking if you can supplement Glutathione for now.

NAC is different than cysteine. Dr. Jill said that NAC does not convert back to cysteine (Dr. Jill does alot with DS & has done lots of good studies on DS). I am going to email her & ask her some questions on this. I'll let you know what I hear back from her. I've read several good things on NAC (including the article that says it helps deal with the Glut depletion that Acetaminophen causes), but then I'm also kind of skeptical about it. Because Dr. L said that for some unknown reason it increases oxidative stress in DS. I've emailed Dr. L & asked him for anymore info he had on this.

Okay, back to the email here . . . I emailed Dr. Jill & she already responded! She said the following:

"Cysteine is high in the plasma - not clear what intracellular levels are. NAC converts to cysteine inside the cells - I don't think it has been tried in DS kids. "

So, this would again, lead me to have that skeptical feeling about giving NAC. Since it does convert to cysteine inside the cells. She does say it is not clear what the cysteine levels in the cells are, but they are high in the plasma. So, I'd be very skeptical to supplement any cysteine at all (including NAC). Since, giving cysteine *can* be toxic, if it is not needed.

For your question regarding how they have too much cysteine, but not enough glutathione - I was very confused by this too, it didn't make sense at first. But, after you look at the SAM cycle more & what the overexpressed CBS gene is doing it starts to make sense. I asked Ginger (who's a brain when it comes to DS - she used to be on the Einstein-Syndrome list) this same question. She gave a very good answer to it, in simple words, here it is:

"In most people, the “limiting” amino acid (which means the one you have the least of) is cysteine. That is why most stuff you read about glutathione tells you to supplement cysteine to improve your glutathione levels. That is not the case in DS. Because of the CBS gene being on chromosome 21, and being overexpressed (remember, not all genes that are triplicated are turned on, but this one is!) it is busy “stealing” homocysteine from the SAM cycle to make cysteine. That is why there is too much cysteine and not enough SAM in DS.In DS, one of the other amino acids appears to be the limiting one."

So, to answer your question regarding if they are deficient in glycine & glutamic acid - it appears they are deficient in at least one of those. But, not sure which one yet (I'm going to look at this more tomorrow, Lord willing). Ginger wrote a couple articles on the ES website about the SAM cycle, CBS gene, etc. Here's a link to those:

http://www.einstein-syndrome.com/biochemistry_101/hole_bucket.htm

http://www.einstein-syndrome.com/biochemistry_101/wipers_bus.htm

Dr. Jill said that Glutathione creams seem to work pretty good for kids with DS. I'm going to ask her what she thinks of Glut creams that have cysteine in them (I know that cysteine is a component of Glut, but if it is added & not bound to some of the other amino acids).

Dr. Jill just said in her email that Methyl B12 has been shown to raise Glutathione levels & Methyl B12 is really good for kids with DS. I suspect that the reason why Methyl B12 helps raise Glutathione levels is because it is in the methyl group (MeB12 that is). And, the reason why there is high cysteine, with low Glutathione is due to the overexpressed CBS gene creating a messed up SAM (S-adenosyl-methionine) cycle. The S-adenosyl-methionine, methionine, Methyl B12, TMG, Folate, cysteine, etc are all part of a methylation group. The methyl donors play a huge role in the body. So, it looks like since Glutathione is, in a way, related to the methyl cycle, that's why Methyl B12 would help with raising Glutathione levels.

There's a really good book that covers this whole Methyl/methylation process really well & in not too technical of terms. It's called Methyl Magic by Craig Cooney. Ginger recommended it to us & it really is a book worth getting. Here's a review on it from LEF - http://www.lef.org/magazine/mag99/sept99_review.html . You can order it from Amazon (http://www.amazon.com/gp/product/0836235851/sr=8-1/qid=1154323442/ref=pd_bbs_1/102-3992125-0682531?ie=UTF8) .

So, it appears that the best ways to help raise Glutathione levels are either by supplementing Glutathione itself (cream or orally or both) and/or Methyl B12.

Hope this helps! Feel free to email with any more questions, etc!

Qadoshyah

From: Sharon

Sent:

Hoppin' Herd of Hares

Qadoshyah,

Thanks for this. Ty is out of surgery, but doctor did not approve Motrin for use until Sunday night.... Before that Tylenol was really her only suggestion. I mentioned this issue, she looked at the abstracts, and asked if it would be possible to supplement Glutathione while on it for a few days. So...that is where we're at.

On this article that you sent, it says "the depletion is overcome by the administration of N-acetylcysteine".

I looked up N-acetylcysteine... and read this article http://www.benbest.com/nutrceut/NAC.html. Now, I am just sarting to try to figure this all out, and get familiar with the terms, so most of it is difficult for me to understand. However, I am wondering how N-acetylcysteine helps kids with DS. Since you previously stated that kids with DS have high levels of cysteine, and should not supplement, and N-acetylcysteine is L-Cysteine plus an acetyl (-CO-CH3) group attached to the amino (NH2) group. OK....so...how does having too much cysteine play into this? Wouldn't adding N-acetylcysteine be aggravating that problem to a certain extent?

"Glutathione (GSH, L-gamma-glutamyl-L-cysteinylglycine) is the predominant anti-oxidant in the aqueous cytoplasm of cells. Virtually all cells require glutathione for viability and function. Glutathione is synthesized from three amino acids in a two-step process, beginning with the combination of glutamic acid & cysteine and ending with the addition of glycine. The liver & lungs are the primary sites of glutathione synthesis. Glycine & glutamic acid are plentiful in cells, so it is the availability of cysteine that controls the reaction rate. "

How does the above bold statement play into this? DS children have TOO much cysteine...is it not "available cysteine"? Or is it just...too much. And, if there is too much cysteine, but not enough glutathione...are they deficient in Glycine and glutamic acid? Sheesh, this is confusing.

"Oral supplementation with N-AcetylCysteine (NAC) provides an alternate means of boosting intracellular glutathione via elevated intracellular cysteine. NAC is rapidly absorbed after oral administration and reaches a maximum plasma level in 2-3 hours, with a half-life of about 6 hours. NAC readily enters cells and is hydrolyzed to cysteine

OK, so if NAC is hydrolyzed to cysteine...why would we want to do that? If there already is too much cysteine? Is the cysteine that kids in DS have not "intracellular cysteine?

Qadoshyah

*Got Down Syndrome?

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