This post kinda works on the requests for a Methylation 101 to be started here. I have been looking at my mutations, and I sure would like some input on if I am on the right track or not. I thought about whether this should be a private post or not, I just didn't want others to miss out on any information that could be helpful to them. Even if we all don't have the same mutations. I'm not asking for a diagnosis, just probabilites or areas in which attention might be needed considering this or that.
My only two +/+ mutations are the MAO-A and the MTHFR C677T.
The other mutations of any consequence are heterozygous, +/- and include:
CBS A360A
ACAT1-02
VDR Bsm/Taq
VDR fok
COMT L136L
MTRR
MTR
SHMT
Let me see if I understand this correctly, and for pete's sake, if I make a wrong statement, please correct it? I make many statements but they are also questions, looking for any input I can possibly get from anyone.
In a condensed form, my homework for each are as follows:
The MTHFR and you can add the vowels because I use them, is a down regulation, and with each +, becomes more of an issue. So a +/+ is a severe down regulation in which the basic purpose of the MTHFR is to make folate by converting 5,10 Mehtylene THF to 5 methyl THF.
SHMT is also a down regulation, and is what actually converts THF to 5,10 Methylene THF, the intermediate step before MTHFR.
An MTR mutation is an upregulation, in which it results in it always being on so it grabs every Hcy and 5 methylfolate molecule it can get ahold of and processes them directly to methionine and THF.
So if the above is correct, then due to my MTR mutation, not only is this pumping more THF in which SHMT cannot convert, nor can MTHFR convert, so I am overloaded with methionine and folic acid and severely deficient in 5 methylfolate, also called metafolin?
Since I only have a +/-, I realize the severity wouldnt be as much as if they were +/+ on all three fronts.
So whats happening then with SAMe and thymadine synthase? And due to the SHMT downregulation, am I making adequate purines?
The ACAT1-02 mutation can be the initial cause of Vitamin B12 deficiency, or is atleast associated with that? I dont know much about this particular mutation, except that it is involved in cholesterol production, of which mine is so very low, I dont even register at the low end of the scale. I believe it is also involved in biological production of energy but by which mechanism, I have no clue. And where is it located on a methylation cycle diagram?
With the MTRR mutation also in the B cycle end, would result in a double whammy effect on Vitamin B12 deficiency, because I cant make as much as I should, and any methyl B12 I might be making, gets sucked up by the upregulation of MTR and pumped right back to THF.
A COMT +/- would mean the propensity for excess methyl groups to exist, but in this case, my VDR Bsm/Taq +/- and my VDR fok +/- would actually result in my COMT acting like a COMT -/-. I also understand the L136L mutation is not considered to be a down regulation, and may perhaps be a compensatory mutation, or somewhat more beneficial than the others in COMT.
Soooo. A downregulation of MTRR and an upregulation of MTR =
low B12, high THF, low 5,10 Methylene THF.
???
The CBS mutation, is an upregulation, in which will drain methyl groups, and in consideration of the above, may explain my high tolerance to methyl groups?
What effects might all this have on my BH4 and urea cycle? I do have high ammonia that I have been fighting for quite sometime. I just cut out a big chunk of protein out of my diet, and am taking Yucca when I do eat protein.
So
COMT +/- and VDR +/- will behave as COMT -/- individual and are considered compensatory mutations. (Complimentary)
MTRR, regenerates methyl B12 and it is this mutation that leads to the greatest need to supplement methyl B12.
MTRs purpose is to regenerate folate.
VDR Bsm/Taq and fok are related to the neurotransmitters. I would like some more info on this, I dont have much on this. And isnt COMT involved with them as well, and how does my particular mutation fit in with the neurotransmitters. And then how do I fit that all in with the MAO-A +/+ mutation?
All the help I can get is so much appreciated. I tend to make statements as well, but actually most are questions and begging for feedback. TIA.
Laurie
My only two +/+ mutations are the MAO-A and the MTHFR C677T.
The other mutations of any consequence are heterozygous, +/- and include:
CBS A360A
ACAT1-02
VDR Bsm/Taq
VDR fok
COMT L136L
MTRR
MTR
SHMT
Let me see if I understand this correctly, and for pete's sake, if I make a wrong statement, please correct it? I make many statements but they are also questions, looking for any input I can possibly get from anyone.
In a condensed form, my homework for each are as follows:
The MTHFR and you can add the vowels because I use them, is a down regulation, and with each +, becomes more of an issue. So a +/+ is a severe down regulation in which the basic purpose of the MTHFR is to make folate by converting 5,10 Mehtylene THF to 5 methyl THF.
SHMT is also a down regulation, and is what actually converts THF to 5,10 Methylene THF, the intermediate step before MTHFR.
An MTR mutation is an upregulation, in which it results in it always being on so it grabs every Hcy and 5 methylfolate molecule it can get ahold of and processes them directly to methionine and THF.
So if the above is correct, then due to my MTR mutation, not only is this pumping more THF in which SHMT cannot convert, nor can MTHFR convert, so I am overloaded with methionine and folic acid and severely deficient in 5 methylfolate, also called metafolin?
Since I only have a +/-, I realize the severity wouldnt be as much as if they were +/+ on all three fronts.
So whats happening then with SAMe and thymadine synthase? And due to the SHMT downregulation, am I making adequate purines?
The ACAT1-02 mutation can be the initial cause of Vitamin B12 deficiency, or is atleast associated with that? I dont know much about this particular mutation, except that it is involved in cholesterol production, of which mine is so very low, I dont even register at the low end of the scale. I believe it is also involved in biological production of energy but by which mechanism, I have no clue. And where is it located on a methylation cycle diagram?
With the MTRR mutation also in the B cycle end, would result in a double whammy effect on Vitamin B12 deficiency, because I cant make as much as I should, and any methyl B12 I might be making, gets sucked up by the upregulation of MTR and pumped right back to THF.
A COMT +/- would mean the propensity for excess methyl groups to exist, but in this case, my VDR Bsm/Taq +/- and my VDR fok +/- would actually result in my COMT acting like a COMT -/-. I also understand the L136L mutation is not considered to be a down regulation, and may perhaps be a compensatory mutation, or somewhat more beneficial than the others in COMT.
Soooo. A downregulation of MTRR and an upregulation of MTR =
low B12, high THF, low 5,10 Methylene THF.
???
The CBS mutation, is an upregulation, in which will drain methyl groups, and in consideration of the above, may explain my high tolerance to methyl groups?
What effects might all this have on my BH4 and urea cycle? I do have high ammonia that I have been fighting for quite sometime. I just cut out a big chunk of protein out of my diet, and am taking Yucca when I do eat protein.
So
COMT +/- and VDR +/- will behave as COMT -/- individual and are considered compensatory mutations. (Complimentary)
MTRR, regenerates methyl B12 and it is this mutation that leads to the greatest need to supplement methyl B12.
MTRs purpose is to regenerate folate.
VDR Bsm/Taq and fok are related to the neurotransmitters. I would like some more info on this, I dont have much on this. And isnt COMT involved with them as well, and how does my particular mutation fit in with the neurotransmitters. And then how do I fit that all in with the MAO-A +/+ mutation?
All the help I can get is so much appreciated. I tend to make statements as well, but actually most are questions and begging for feedback. TIA.
Laurie