-------------------- --Keep an open mind about everything. Also, remember to visit ACTIVISM (we can change things together). Posts: 5418 | From earth | Registered: Mar 2011
| IP: Logged |
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
This genetic defect - MTHFR (20% of the population has this problem in one form or another)...causes the inability to break down folic acid/folate (B9)
to its useful form which is used
to "recyle" methionine via the "remethylation pathway" which
LOWERS homocysteine.
Backing up a second...
When we eat protein, we get methionine (Methyl = CH3) which converts to homocysteine (we need methionine!). Homocysteine is toxic and has to be recycled back to methionine (remethylation pathway) or made into other essential things (transsulfuration pathway).
The other pathway to lower homocysteine is called the Transsulfuration pathway. I'll talk more about THAT pathway and how Bb is involved in a minute.
B9 works with B12 and an enzyme called BHMT (Zinc dependent) to lower homocysteine levels.
Bb MAKES homocysteine (documented)!!! via a REVERSE transsulfuration pathway...
Write the word homocysteine down.
Put an arrow down from that word.
Next to that arrow, put B6 (yes, the vitamin) on one side and CBS (an enzyme) on the other side of the arrow.
Now draw another arrow down
below that arrow write the word, crystathionine
Draw another arrow down below that word.
Write the word cysteine.
From cysteine
Draw 3 arrows that fork off...(one towards the left, one straight down and one towards the right).
Below those arrows, L->R write: Taurine (which lowers cholesterol), GSH = glutathione (below the straight arrow down) and Sulfate (off to the right).
Bb looks to reverse the process...from cysteine up to homocysteine.
This is called REVERSE transsulfuration pathway.
Meanwhile it's a "fight" as WE try to lower homocysteine -> cysteine -> taurine, GSH and sulfate via using B6 and CBS and recycle it.
Bb we KNOW, for fact, needs N acetylcysteine.
So do we!
Addition of GlcNAc (= N acetylcysteine) to phosphofructokinase 1 (PFK1) - the rate limiting enzyme for glycolysis...
*inhibits the glycolytic pathway.*
This redirects cell metabolism to the pentose phosphate pathway—
boosting *nucleotide synthesis*
and helping cells adapt to oxidative stress.
Because the mechanism is dynamic and reversible, cancer cells (me...also) can rapidly alter metabolism in response to changes in the tumor microenvironment.
Sublingual B12 was (once tried) not a good thing for my son and
recently not a good thing for a friend - bad reactions.
B12 works with MS (Methionine synthase - an enzyme)also in the "remethylation pathway"...
Research: Candida and MS (Methionine synthase) Candida and N acetylcysteine (Bb's fav. food)
Posts: 9481 | From Sunshine State | Registered: Mar 2001
| IP: Logged |
Razzle
Frequent Contributor (1K+ posts)
Member # 30398
posted
The form of B12 may determine one's tolerance of B12.
Cyanocobolamin has to be split into the cyano- part and the cobolamin (B12) part. Then the cyano part has to be detoxed. Not everyone's body is efficient at doing this, thus a large dose of the cheap synthetic cyanocobolamin would certainly result in side-effects.
Also, those who are over-methylated, have CBS mutations, or who have COMT mutations without VDR mutations, need to use hydroxycobolamin or adenosylcobolamin instead of methylcobolamin to avoid getting too many methyl groups.
And finally, because methylcobolamin promotes methylation and thus glutathione production, sometimes the "side-effects" are actually symptoms of toxin mobilization. This is why one should start with small amounts of methylated B vitamins and slowly work your way up, instead of starting at the max/recommended dose.
And a comment about those who say they didn't notice anything different from supplementing methyl-folate (or other methylation supplements):
If you already methylate well, there would be nothing 'new' to notice.
Also, the types of things good methylation (and homocysteine reduction) results in are not things one would necessarily "feel" right away - this is more about _prevention_ of future problems (heart disease, plaque buildup in the arteries, Alzheimer's, etc.).
-------------------- -Razzle Lyme IgM IGeneX Pos. 18+++, 23-25+, 30++, 31+, 34++, 39 IND, 83-93 IND; IgG IGeneX Neg. 30+, 39 IND; Mayo/CDC Pos. IgM 23+, 39+; IgG Mayo/CDC Neg. band 41+; Bart. (clinical dx; Fry Labs neg. for all coinfections), sx >30 yrs. Posts: 4167 | From WA | Registered: Feb 2011
| IP: Logged |
droid1226
Frequent Contributor (1K+ posts)
Member # 34930
posted
i've been drawing these out for my dr and my own purposes, plus i know MTHFR is the way to health(at least for me) so i'm really trying to understand it
i only understand half of what marnie says, so if i'm wrong please tell me where. and if u have any more diagrams for understanding MTHFR...please let me know. i'm really interested in this pathway.
Because that picture shows where MTHFR fits in.
Posts: 9481 | From Sunshine State | Registered: Mar 2001
| IP: Logged |
lymie_in_md
Frequent Contributor (1K+ posts)
Member # 14197
posted
This is the first of three figures:
Homocysteine metabolic pathways. Dietary methionine is converted to the methyl donor S-adenosylmethionine (SAM) and is demethylated to S-adenosylhomocysteine (SAH) and homocysteine. In the transsulfuration pathway, homocysteine is converted to cystathionine by the enzyme cystathionine -synthase (CBS) and the cofactor vitamin B6 (pyridoxyl phosphate). Once formed from cystathionine, cysteine can be utilized in a number of cellular functions, including protein synthesis and glutathione (GSH) production. Homocysteine can also be remethylated through the folate cycle. This pathway requires the enzyme methionine synthase (MS) and vitamin B12 as well as the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) and folic acid, which enters the cycle as tetrahydrofolate (THF). In liver and kidney, homocysteine is also remethylated by the enzyme betaine homocysteine methyltransferase (BHMT), which transfers a methyl group to homocysteine via demethylation of betaine to dimethylglycine (DMG)
-------------------- Bob Posts: 2150 | From Maryland | Registered: Dec 2007
| IP: Logged |
lymie_in_md
Frequent Contributor (1K+ posts)
Member # 14197
posted
Second figure :
ER stress and the unfolded protein response (UPR). The UPR is regulated in eukaryotes by the proximal sensors IRE-1, ATF-6, and PERK. Activation of these sensors occurs following their dissociation from GRP78 in response to ER stress. Once activated, the UPR functions as an integrated, intracellular signaling pathway to attenuate protein translation, increase ER chaperone expression, and enhance degradation of unfolded proteins via the proteosome
-------------------- Bob Posts: 2150 | From Maryland | Registered: Dec 2007
| IP: Logged |
lymie_in_md
Frequent Contributor (1K+ posts)
Member # 14197
posted
Last figure :
Atherosclerotic lesions in the aortic root of apoE-deficient mice fed a control diet or a high methionine diet to induce HHcy. Lesion sizes in mice fed high methionine diet were significantly larger, compared to mice fed control diet. Sections were stained with Orcein to reveal the elastic lamina (kindly provided by Ji Zhou and Erling Falk)
-------------------- Bob Posts: 2150 | From Maryland | Registered: Dec 2007
| IP: Logged |
lymie_in_md
Frequent Contributor (1K+ posts)
Member # 14197
posted
Marnie -- take a look at the tipping point article let me know what you think.
I thought the last figure 3 where you see the wall is collapsing, that's either inflammation or plaque or a combination of both. And how the walls are thinning. If it is plaque the body might be making a conscious decision to protect the thinning walls. This is a case of epigentics as well, where the body is twiddling gene expression.
BTW : Marnie, I know you'll connect all the dots
Bob
-------------------- Bob Posts: 2150 | From Maryland | Registered: Dec 2007
| IP: Logged |
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
I knew I could count on a computer expert!
Will research later.
I think Bb's phosphodiesterases (PDE6 componenet= PDEa and PDEb) are core proteins to trigger GTP -> cGMP.
Meanwhile rhodopsin -> increased GTP.
Then Bb's proteins kick in ...GTP -> cGMP.
But...rhodopsin maybe THE protective enzyme.
It contains mannose and n-acetylglucosamine - binds.
If the WFL upregulates rhodopsin in order to see in the dark when it hunts for insects to eat, does it (rhodopsin) rob Bb of mannose and n-acetylglucosamine
OR
Does Bb steal mannose (which we know Bb needs) and n acetylglucosamine (which we know Bb needs)
-> less rhodopsin...not enough GTP?
Rhodopsin = GTP made, Bb's PDE6 components i.e., (PDEa and PDEb) look to then -> GTP to cGMP.
Inhibiting phosphodiesterases is ...well ya know, Bob. :-)
Looks like Bb doesn't like to be "bleached" (in more ways than one).
Posts: 9481 | From Sunshine State | Registered: Mar 2001
| IP: Logged |
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Here is one of my MTHFR files...
MTHFR
Genes are protein chains of amino acids in a specific arrangement.
The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase.
This enzyme plays a role in processing amino acids, the building blocks of proteins.
Methylenetetrahydrofolate reductase is important for a chemical reaction involving forms of the B-vitamin folate (also called folic acid or vitamin B9).
Specifically, this enzyme converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate.
This reaction is required for the multistep process that converts the amino acid homocysteine to another amino acid, methionine.
The body uses methionine to make proteins and other important compounds.
As many as 20% of the population has inherited a defective copy of the gene that makes this MTHFR, a condition that makes it harder for folate to get into the brain.
This meta-analysis demonstrates an association between the MTHFR C677T variant and depression, schizophrenia, and bipolar disorder, raising the possibility of the use of folate in treatment and prevention.
It is also linked to anxiety and ADHD.
Folate in the brain is the necessary building block for many neurotransmitters (including serotonin), which helps regulate our MOODS!
MTHFR takes folate (vitamin B9) and methylates (converts) it into methylfolate (5-methylTHF).
Hardly seems like a big deal, does it? Yet, if you belong to an autism, Pandas, Lyme or chronic fatigue group, you’ve probably noticed a big buzz around this thing called methylation.
While the past decade has seen MTHFR studied in terms of cardiovascular disease and cancer, it turns out it might also be a very big deal for those raising kids with developmental, neurological or behavioral symptoms and for those fighting chronic infections.
At least 40 mutations in the MTHFR gene have been identified in people with homocystinuria. Most of these mutations change single amino acids in methylenetetrahydrofolate reductase.
These changes impair the function of the enzyme, and some cause the enzyme to be turned off (inactivated).
Other mutations lead to the production of an abnormally small, nonfunctional version of the enzyme.
Without functional methylenetetrahydrofolate reductase, homocysteine cannot be converted to methionine.
As a result, homocysteine builds up in the bloodstream, and the amount of methionine is reduced.
Some of the excess homocysteine is excreted in urine.
Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.
Several variations (polymorphisms) in the MTHFR gene have been associated with an increased risk of neural tube defects (NTDs), a group of birth defects that occur during the development of the brain and spinal cord.
Anencephaly is one of the most common types of neural tube defect. Affected individuals are missing large parts of the brain and have missing or incompletely formed skull bones.
Polymorphisms in the MTHFR gene are also associated with an increased risk of spina bifida, another common type of neural tube defect.
In people with this condition, the bones of the spinal column do not close completely around the developing nerves of the spinal cord. As a result, part of the spinal cord may stick out through an opening in the spine, leading to permanent nerve damage. (Hence the recommendation women supplement folic acid during pregnancy)
Polymorphisms in the MTHFR gene have also been studied as possible risk factors for a variety of common conditions.
These include heart disease, stroke, high blood pressure (hypertension), high blood pressure during pregnancy (preeclampsia), an eye disorder called glaucoma, psychiatric disorders, and certain types of cancer
To counter an inability to process folic acid to its useful form, doctors prescribe Deplin or a person can take over-the-counter Folo Pro.
DNA testing can pick up a problem.
This is what they look for: C677T and A1298C,
If a person has two copies (homozygous) of MTHFR C677T, or has one copy of C677T and one of A1298C, then it is likely that elevated homocysteine levels are due to these inherited mutations, or that the mutations are contributing to them.
Two copies of A1298C are *not* typically associated with increased homocysteine levels.
If the MTHFR mutation test is negative, then the C677T and A1298C mutations were not detected and the tested person's elevated homocysteine level is likely due to another cause.
Other, more rare MTHFR genetic mutations will not be detected with typical testing.
People who have elevated homocysteine levels may be at an increased risk of developing premature cardiovascular disease (CVD) and/or thrombosis, but many, including those with MTHFR mutations, will never develop CVD or thrombosis.
The role of homocysteine in cardiac risk assessment is still in the process of being determined.
Besides MTHFR mutations, there are other causes of elevated homocysteine levels,
including deficiency of vitamins B6, B12, and/or folate;
these vitamins are required for homocysteine metabolism.
The MTHFR mutation may not be present with these acquired, as opposed to inherited, causes of elevated homcysteine.
For MTHFR mutations, the C677T variant results in substitution of the amino acid alanine for valine.
The A1298C variant results in an alanine substitution (versus a glutamine). The C677T valine substitution results in a less active form of the MTHFR enzyme.
The MTHFR enzyme is involved in folate metabolism. Because of this, those who have MTHFR mutations and take drugs that affect folate metabolism, such as methotrexate, may be more likely to experience toxicity.
An MTHFR mutation test may be performed for a person who is prescribed methotrexate in order to adjust dosages and reduce risk of toxicity.
The cogs in this picture turn in your body billions of times per second. But quick, before your eyes glaze over, find the MTHFR in the middle of the picture. Got it?
Hey, Bob...need help in posting the picture shown here:
-------------------- Bob Posts: 2150 | From Maryland | Registered: Dec 2007
| IP: Logged |
Marnie
Frequent Contributor (5K+ posts)
Member # 773
posted
Bob...YUP! Thanks! Tipping point? You mean genetics PLUS environment (pathogens exposure)...oh, yea!
Recovery may be more difficult and more complex for those with some genetic differences, but
NOT IMPOSSIBLE!
Posts: 9481 | From Sunshine State | Registered: Mar 2001
| IP: Logged |
lymie_in_md
Frequent Contributor (1K+ posts)
Member # 14197
posted
Some day a discovery of how our conscious and subconscious mind has the keys and thereby control over all the genetic toggles which influence genetic expression. Of course these toggles are epigenetics and there maybe other genetic modifiers not yet discovered. We don't know a great deal about how it all functions.
The environment, supplements, bioenergy, the etherial plane, frequencies of all kinds are just information. The information is either good information (ice cream, fire works) or bad information (tick bites, bad news).
The tipping point is an article I created a topic for and posted, it kind of ties with genetic expression. In that it talks about giving the body too much information of a certain kind. Like, giving the body too much magnesium at once or to much of a frequency or too much light to help the body resolve a shortage. I think a method of too much information is the SALT / C protocol (could be good or bad). One could fashion a tick bite as too much information for the genetics of some to handle while other are ok. The same could be said of a poisonous spider bite, it's not the amount of venom, but the overwhelming information. Too much of something good might get rid of something bad.
So you are right, NOT IMPOSSIBLE
-------------------- Bob Posts: 2150 | From Maryland | Registered: Dec 2007
| IP: Logged |
The Lyme Disease Network is a non-profit organization funded by individual donations. If you would like to support the Network and the LymeNet system of Web services, please send your donations to:
The
Lyme Disease Network of New Jersey 907 Pebble Creek Court,
Pennington,
NJ08534USA http://www.lymenet.org/
UBBFriend: Email this page to someone!
![[Smile]](smile.gif)
![[Wink]](wink.gif)
Printer-friendly view of this topic