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Methyl Trapping and the Cobalamins

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by pgoody, Apr 30, 2013.

  1. pgoody

    pgoody

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    I know there are many people who advocate the use of both methyl b12 and methyl folate use simultaneously for the purpose of moving the folate cycle through the methylate homocysteine.

    As far as my understanding goes, 5-methyl THF donates methyl to cobalamin, which becomes methyl cobalamin, and then that methyl is transferred to homocysteine to form methionine.

    According to many places on this forum, methyl trapping can occur when one is deficient of b12, so 5-mTFH cannot pass its methyl group to cobalamin and be converted back into THF.

    The reason I bring this up is because I was just reading this article about autism in which it states,
    "Methyl-B12: Replaces need for methyl group transfer from 5methylTHF: potential for trapping folate as 5-methyl- THF and reducing synthesis of metabolically active THF".
    Article: (http://www.tacanow.org/wp-content/uploads/2010/07/glutathione-autism-1.pdf)

    In this way it almost sounds as if too much methylb12 will inhibit the passing of methyl from folate because it's already methylated causing trapping. Thoughts on this?

    What the heck is going on inside of a normal person?? What form of cobalamin normally exists in this reaction? It can't be methyl cobalamin. Methyl cobalamin is the RESULT of methyl transfer from 5 mTFH.

    In this textbook "Postgraduate Haemotology" it states that 5- deoxyadenosyl (ado) is the main form of cobalamin in nature and in human tissue". Is this the same as the "adenosyl" form that many of you refer to?
    source:
    (http://books.google.com/booksid=1A6...6AEwBTgU#v=onepage&q=glutathionyl b12&f=false)
  2. Freddd

    Freddd Senior Member

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    Hi Pgoody,

    The idea that methylfolate has to supply a methylgroup to the cobalamin originates with the mistake, CyCbl followed by HyCbl. Having MeCbl negates the NEED for that extra step which was put in to explain how an inactive cobalamin could work even a little bit. It is part of the recycling mechanism so that the same cobalamin molecule can be used over and over so it is more effective. Adenosylcobalamin is the other main form of active b12. It is used in for lipids processing and ATP production and inflammation control. It is the main form in muscle tissue. MeCbl is the main form for the neurology and cell reproduction. However both are needed and they work synergistically together. There are 70 years of research base on CyCbl and HyCbl. Those in no way predict the activity or effectiveness of MeCbl and AdoCbl which are about 100 to 10,000 times as effective as those two inactive cobalamins.
  3. pgoody

    pgoody

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    Freeddd I don't follow this part of your response.

    My interest in this b12 issue originates from the fact that I am interested in trying to methylate "naturally" or in a way that doesn't cause any sort of negative feedback inhibition upstream of MTR or any "bottlenecking" of substrates.

    If you look at this site (http://cble.homestead.com/files/Cble.htm) and many others. They reference cobalamin in other forms, Cob(I, II, and III)alamin aside from methyl, adenosyl, hydroxty etc etc, which makes things yet more confusing.

    From that link I provided, it says:
    "Cleavage of the methyl-cobalt bond of the methylcob(III)alamin intermediate occurs heterolytically so as to leave the cobalamin in the highly reactive cob(I)alamin oxidation state. During the cycling between methylcob(III)alamin and cob(I)alamin, the cofactor may be oxidized to cob(II)alamin with consequent inactivation of the enzyme."

    From what I have gathered, saying that methylcobalamin is the only active form is not entierly accurate (again, only from what I have gathered). If you look at the statement above, cob(I)almin is in a "highly reactive" oxidation state, and it is this form, having been cleaved from the methyl group, that accepts methyl from 5- mTHF and continues the Methionine Synthase cycle. This is indicated on many Methionine Synthase Reductase diagrams.

    To be even more specific about how I am understanding all of this... If one were to ingest ONE unit of methylcobalamin, that cobalamin would methylate homocysteine into methionine and then it would become cob(I)alamin. Since there are so many methylation reactions in the body it would seem more likely that the methylcobalamin is methylating you much more as a reciever of methyl from 5mTHF than by it doning the 1 methyl group that comes preattatched.

    Is there anyway to provide your body with this "cob(I)alamin" which still plays and ACTIVE role in methylation? Is there any supplemental form of cobalamin that represents this oxidative state, which will readily accept at methyl from 5-mTHF? The purpose of this would to 1) avoid a sudden unnatural influx of methylation by allowing the natural process to dictate the process of methylation. 2) so one does not skip the "extra" step of methyl donation from 5 mTHF so that THF can be recylced to form pyurines(?) and DNA.

    Here I found a site that discusses the various points along the entire path of b12 in your body starting from problems ingesting it. (http://emedicine.medscape.com/article/204930-overview#a0104). It seems to me that if an individual were to not have an issue at points CDE or G (refer to the second image in that link) that hydroxy could still be a useful solution.

    Attached Files:

  4. adreno

    adreno 3% neanderthal

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    Tundras of Europa
    I'm not sure I see the problem? Methylcobalamin donates a methyl group to make methionine, and is then ready to accept a methyl group donated from methylfolate.
  5. pgoody

    pgoody

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    Here I'll copy and paste my concerns from my last post:
    1) avoid a sudden unnatural influx of methylation by allowing the natural process to dictate the process of methylation. 2) so one does not skip the "extra" step of methyl donation from 5 mTHF so that THF can be recylced to form pyurines(?) and DNA.

    also: 3) avoid any unnecessary symptoms of overmethylation for those who are COMT +/+

    I've seen the COMT issued mentioned by Ben Lynch and Yasko.
  6. adreno

    adreno 3% neanderthal

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    1) There is no "unnatural influx of methylation". You can have too few, adequate or too many methyl groups. 2) This step isn't skipped, as I explained above. 3) You avoid overmethylation by adjusting the dose of methyl groups, not by changing forms.
  7. Freddd

    Freddd Senior Member

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    Hi Pgoody,

    Cob(I, II, and III)

    Oxidation states. Methylcobalamin has a +1 oxidations state, Adenosylcobalamin I believe is +2 and Cyanocobalamin is +3. Other various forms may also have those same oxidation states. III is the hightest oxidation state from which our body can recover some of the cobalamin for reuse as one of the two active forms. Now this is just an approximate explanation. I've never seen it clearly laid out.
  8. Freddd

    Freddd Senior Member

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    Hi Pgoddy,

    Neither MeCbl or AdoCbl are "used up" by methylation or ATP manufacture, they end up how they started, like a catalyst. MeCbl alternates between methyl donor and methyl receiver until available methyl groups are exhausted or something else shuts it down. Cyanide coming along combines with Cobalamin with a +3 bond that take a relatively lot of energy to recycle. Nitrous oxide permanently oxidizes cobalamin and it can't be reclaimed. Other toxins combine with cobalamin and eliminate it from the body. When in starvation mode there is only recycle mode.
  9. pgoody

    pgoody

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    Freddd, thanks for your explanation. I reattached the image I put in my 2nd response in case you missed it, but I am guessing you have seen this already. This just shows the various oxidation states of cobalamin during before and after MTR and MTRR. I almost didn't post this because I feel so damn ignorant. :whistle:
    hypot.gif

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