A basic explanation of methylation?

sharks

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methylation? What exactly is it? Everyone talks about it in the fourms as if I am suppose to know what it means.

Also when I do read something about methylation, I am linked to a unofficial blog with goblity-gook. No back up with scientific facts what so ever. I almost don't believe that methylation is real and is made up.

Can someone hook me up with basic information?
 

Alvin2

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I actually wondered this too and meant to look into it someday, thanks for posting this thread :thumbsup:
 

Snowdrop

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Heere's one chart showing the methylation cycle . I'm afraid I can't explain but it is real.

 
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The methylation cycle is an extremely complex cycle that creates/converts many different chemicals in the body.

I've discussed it with one of my doctors, who was surprised that I'd even heard of it, and who said that it's something they study in medical school but is so complicated that even most doctors don't really understand it, and most tend to forget about it because they don't use it in day to day practice. It is most definitely a real thing!



This is a quote from a Chris Kresser interview (who I think does a good job of explaining complex medical topics) You can read the transcript of the interview for more info, if you are interested:

Methylation happens when one molecule passes a methyl group, which is a carbon atom linked to three hydrogens, to another molecule, so it’s a pretty basic biochemical process. These reactions that occur when one molecule passes a methyl group to another make things like creatine, carnitine, CoQ10, phosphatidylcholine, melatonin, and tons of other really important substances in the body.

Methylation controls sulfur metabolism, which balances the need for methyl groups, glutathione to control oxidative stress, and other sulfur metabolites like cysteine, taurine, and sulfate. Methylation influences the production of ATP, which is the fundamental energy unit of the cell. If you remember back to your high school biology course, you probably remember ATP. If the cell can’t produce ATP, then there’s going to be inadequate energy in the body, nothing will work well, and you get a breakdown or an impairment of your mitochondrial function. https://chriskresser.com/methylation-what-is-it-and-why-should-you-care/
 

sharks

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The methylation cycle is an extremely complex cycle that creates/converts many different chemicals in the body.

I've discussed it with one of my doctors, who was surprised that I'd even heard of it, and who said that it's something they study in medical school but is so complicated that even most doctors don't really understand it, and most tend to forget about it because they don't use it in day to day practice. It is most definitely a real thing!



This is a quote from a Chris Kresser interview (who I think does a good job of explaining complex medical topics) You can read the transcript of the interview for more info, if you are interested:

Methylation happens when one molecule passes a methyl group, which is a carbon atom linked to three hydrogens, to another molecule, so it’s a pretty basic biochemical process. These reactions that occur when one molecule passes a methyl group to another make things like creatine, carnitine, CoQ10, phosphatidylcholine, melatonin, and tons of other really important substances in the body.

Methylation controls sulfur metabolism, which balances the need for methyl groups, glutathione to control oxidative stress, and other sulfur metabolites like cysteine, taurine, and sulfate. Methylation influences the production of ATP, which is the fundamental energy unit of the cell. If you remember back to your high school biology course, you probably remember ATP. If the cell can’t produce ATP, then there’s going to be inadequate energy in the body, nothing will work well, and you get a breakdown or an impairment of your mitochondrial function. https://chriskresser.com/methylation-what-is-it-and-why-should-you-care/
Thank you for the explination. How does this relate to CFS/ME?

I am not going to the site you supplied. Anyone can make a website and put whatever on it to sell books and suppliments and what not. That is the problem I am having finding any good information.
 

sharks

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There happens to be a lot of good information on that site, which is why I linked it.
What makes this person qualified? How do we know this information is valid? When I google "Methylation" I get Methylation as related to DNA. Any information of Methylation as related to health or CFS comes from websites anyone can make.

My concern is that anyone that can make a website and be at a top of a search engine. I feel that this strips the validity of this disease and futher continues the negative stigma surrounding it.
 
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I've been reading Chris Kresser's articles and interviews for many years, and have fact-checked much of what he says. I have never found inconsistencies and I believe him to be a reputable source of health information. You have to analyze what any person or website claims and determine for yourself the validity.
 

NotThisGuy

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How about you just look for information in this forum?

http://forums.phoenixrising.me/index.php?threads/documents-by-rich-van-konynenburg-parts-1-7.11488/

here you have some informations from r.v. konynenburg.
What qualifies him? Read his biographie and you will know.

You can also google cheney, he is here on this forum as well just like rich was.

There is some research behind this, but the problem is most people don't want to read the scientific papers.
If you don't want information from a website everyone can make, you have do dive into scientific papers. (pubmed etc.)
The summary of rich contains very much references, so have fun reading.
 

alicec

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If you google one carbon metabolism you might find more information which is not trying to cash in on trendy internet chatter (not that I think Chris Kesser is trying to do this - I agree with @Basilico, he is usually a reliable source of information).

For this is what methylation is all about, the transfer of single carbon units (methyl groups) which are used in a wide variety of biosynthetic processes in the body.

At the heart of 1C transfer is the folate cycle which mediates three biosynthetic pathways, de novo synthesis of purines, thymidylate synthesis and the remethylation of homocysteine to form methionine (a B12-dependant reaction).

Here is an illustration of these pathways which is derived from this paper.

Methionine in turn is a precursor for the synthesis of S-adenosylmethionine (AdoMet or SAM), a cofactor and methyl group donor for numerous methylation reactions, including the methylation of cytosine bases in DNA, histones, RNA, neurotransmitters, and other small molecules, phospholipids, and other proteins.

S
-adenosylmethionine–dependent methylation reactions serve to regulate fundamental biological processes, including gene transcription, mRNA translation, cell signaling, protein localization, and the degradation of small molecules.

The primary source of one-carbons for cytoplasmic one-carbon metabolism comes from formate that is derived from mitochondrial one-carbon metabolism and the ultimate source of formate is the amino acid serine.

Here, here and here are university websites which illustrate the pathways in different ways. Sometimes people find different approaches more understandable.

Here is a paper which quantitates the relative importance of the different pathways, concluding that

The available evidence indicates that the quantitatively most important pathways for S-adenosylmethionine–dependent transmethylation in mammals are the syntheses of creatine by guanidinoacetate methyltransferase, of phosphatidylcholine by phosphatidylethanolamine methyltransferase, and of sarcosine by glycine N-methyltransferase.
Here is just old review which canvasses some of the ways these pathways are thought to be relevant to various health conditions. It is old but it does set things out clearly.

How does all this relate to ME/CFS?

We don't really know, though people have various theories, including Rich who you have already been directed to. Certainly many people on PR have reported benefit from folate/B12 supplements.

The recent work of Naviaux might provide some clues about this. He found widespread metabolic derangement in ME/CFS patients, all of which were either directly regulated by redox or the availability of NADPH.

1C metabolism is directly related to this since transulfuration produces cysteine, the rate-limiting step in synthesis of the ultimate redox controller glutathione, while one of the folate cycle enzymes (MTHFD2L) is an important source of NADPH.
 

PinkPanda

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Here is a picture of the methylation cycle I found very helpful.
http://heliosphan.org/methioninecycle/methionine-cycle-rev4.png

Methylation depends on a lot of cofactors and the enzyme mutations MTHFR and MTRR/MTR in the methylfolate and methylcobalamin metabolism may reduce methylation.
I guess that's why the methylation cycle gathered some attention. SAM-e/ methyl groups are very important in the metabolism and there's a good chance that they aren't being produced enough in ME/CFS and other illnesses.
 

alicec

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I thought afterwards that my reference to the folate cycle enzyme MTHFD2L might be confusing since it is not shown in any of the links I gave.

To make a complicated picture even more complicated, you need to realise that the folate cycle occurs also in mitochondria and uses slightly different enzymes from the illustration I linked for cytoplasmic and nuclear compartments.

MTHFD2L operates in the mitochondrion only.

This figure from this paper shows the cytoplasmic and mitochondrial pathways in parallel.

In the cytoplasm, MTHFD1 is tri-functional. Reactions 1-3 in the figure are all carried out by a single enzyme with 3 different capabilities incorporated into a single protein.

In the mitochondrion, however, the three functions have been split. MTHFD1L carries out one function (reaction 1m) while MTHFD2L carries out the other two (reaction 2m and 3m). There is another enzyme, MTHFD2, which has a similar function to MTHFD2L, but it is found in very restricted circumstances. MTHFD2L is the enzyme which normally performs this function in adult cells.

The paper has a good explanation of how the folate cycle operates (I have broken up the text for easier reading).

Tetrahydrofolate (THF)3-dependent 1-carbon metabolism is highly compartmentalized in eukaryotes, with THF-dependent enzymes found in mitochondria, cytoplasm, and nuclei (1, 2).

The 3-carbon of serine is the major 1-carbon donor in most organisms, including humans (3), and THF can be charged with this 1-carbon unit in both the cytoplasmic and the mitochondrial compartments via serine hydroxymethyltransferase (Fig. 1, reactions 4 and 4m), resulting in the formation of 5,10-methylene-THF (CH2-THF).

Cytoplasmic CH2-THF can be reduced to 5-methyl-THF (CH3-THF) (reaction 6) for entry into the methyl cycle, it can be oxidized to 10-formyl-THF (10-CHO-THF) (reactions 3 and 2) for purine synthesis, or it can be used for nuclear thymidylate (dTMP) synthesis (reaction 10) (2).

The other product of the serine hydroxymethyltransferase reaction, glycine, can be metabolized by the mitochondrially localized glycine cleavage system (reaction 5), producing CH2-THF from its 2-carbon (4, 5).

CH2-THF, from either serine or glycine, can be oxidized to 10-CHO-THF by mitochondrial versions of reactions 3 and 2. 10-CHO-THF can either be converted to formate and THF by 10-formyl-THF synthetase (reaction 1m) or oxidized to form CO2 and THF by 10-formyl-THF dehydrogenase (reaction 11) (6, 7).

The cytoplasmic and mitochondrial compartments are metabolically connected by transport of serine, glycine, and formate across the mitochondrial membranes, supporting a mostly unidirectional flow (clockwise in Fig. 1) of 1-carbon units from serine to formate and on to methionine. In fact, it appears that under most conditions, the majority of 1-carbon units for cytoplasmic processes are derived from mitochondrial formate (6,17).
 

sharks

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If you google one carbon metabolism you might find more information which is not trying to cash in on trendy internet chatter (not that I think Chris Kesser is trying to do this - I agree with @Basilico, he is usually a reliable source of information).

For this is what methylation is all about, the transfer of single carbon units (methyl groups) which are used in a wide variety of biosynthetic processes in the body.

At the heart of 1C transfer is the folate cycle which mediates three biosynthetic pathways, de novo synthesis of purines, thymidylate synthesis and the remethylation of homocysteine to form methionine (a B12-dependant reaction).

Here is an illustration of these pathways which is derived from this paper.

Methionine in turn is a precursor for the synthesis of S-adenosylmethionine (AdoMet or SAM), a cofactor and methyl group donor for numerous methylation reactions, including the methylation of cytosine bases in DNA, histones, RNA, neurotransmitters, and other small molecules, phospholipids, and other proteins.

S
-adenosylmethionine–dependent methylation reactions serve to regulate fundamental biological processes, including gene transcription, mRNA translation, cell signaling, protein localization, and the degradation of small molecules.

The primary source of one-carbons for cytoplasmic one-carbon metabolism comes from formate that is derived from mitochondrial one-carbon metabolism and the ultimate source of formate is the amino acid serine.

Here, here and here are university websites which illustrate the pathways in different ways. Sometimes people find different approaches more understandable.

Here is a paper which quantitates the relative importance of the different pathways, concluding that



Here is just old review which canvasses some of the ways these pathways are thought to be relevant to various health conditions. It is old but it does set things out clearly.

How does all this relate to ME/CFS?

We don't really know, though people have various theories, including Rich who you have already been directed to. Certainly many people on PR have reported benefit from folate/B12 supplements.

The recent work of Naviaux might provide some clues about this. He found widespread metabolic derangement in ME/CFS patients, all of which were either directly regulated by redox or the availability of NADPH.

1C metabolism is directly related to this since transulfuration produces cysteine, the rate-limiting step in synthesis of the ultimate redox controller glutathione, while one of the folate cycle enzymes (MTHFD2L) is an important source of NADPH.
Thank you! This is what I am looking for.