OAT, PLEASE INTERPET

[alicec]

This seems important to me as my Krebs cycle is "stuffed." Would my nonexistent AKG have something to do with a faulty limpoic acid metabolism? Supplement with ALA?

The quote is in turn linking all that and a host of other problems to lack of active B2 (FAD).

 

[alicec]

I wonder if this would be the case for supplementing with 5HTP?

It could well be. Is it losing effect? Pulsing might be better. For other amino acids it would depend on what they are.

 

[alicec]

Going back to the folate cycle and the little cycle

The little cycle is showing that conversion of 10 formylTHF to THF can happen in three separate ways - ie the formyl group can be used in three separate reactions.

In one, ATP is generated - in the overall scheme of things, this is a very minor source of ATP but might be used more when more usual ways are blocked.

In another, NADPH is generated - not the main source of NADPH in the cell but an important contributor.

In another, purine synthesis occurs.

Which of the three paths is favoured depends on the balance of many other things.

 

[Valentijn]

So there are 4 nucleobases but are only present in 3 nucleobase combinations in the exons (the coding section of the gene)? Each 3 letter combination produces a certain enzyme or amino acid?

The exons on a gene will have dozens of nucleobases, but each set of three nucleobases will spell out an amino acid. Amino acids are strung together in the right order to create a specific enzyme.

I think I'm beginning to understand. So if an amino acid is missing a little bit of the code at the end it doesn't affect the amino acid from doing its job?

It would be the enzyme doing a job, even if it's missing a few amino acids at the end due to the DNA code stopping it prematurely.

So the 3 letter combination produces an amino acid and a combination of amino acids produces an enzyme?

Exactly!

If in your example cysteine TGC or TGT is changed to TGA (a stop command?) it prevents the gene from creating the enzyme? Is it safe to presume A nucleobases are stop commands?

There are 4 nucleobases (A C G T) which can be put together in any three-nucleobase combination ("codon") to form an amino acid, so there are 64 (4 x 4 x 4) possible unique codons. There are only 20 amino acids which can be created by our DNA, so there are up to 6 different codons (combinations) which can create each amino acid, though for some amino acids there's only one codon which creates it.

Three of those codons are a "stop" command, which simply stops the creation of the amino acids where ever it is located on the gene. The rest of the enzyme, up to that point, will have the normal sequence of amino acids. If it doesn't "stop" until after the important bits, that truncated enzyme might still be able to work normally or pretty well.

So the "A" on the end isn't indicative of it becoming a stop command, unless the first two nucleobases in the codon are TA or TG. Here's an amino acid wheel which shows the codons creating each amino acid or stop sequence (colored bits are non-adjacent codons which have the same outcome):

 

[Jimbo39]

The quote is in turn linking all that and a host of other problems to lack of active B2 (FAD).

FAD is synthesized from riboflavin (vitamin B2) and ATP. The gastrointestinal absorption, distributio

I don't know how I missed this. Would supplementing with more than Freddd's recommended dosage (B2) lead to any kind of paradoxical reaction?

I can see the validity of supplementing with cofactors to avoid downregulation and feedback inhibition.

 

[Jimbo39]

It could well be. Is it losing effect? Pulsing might be better. For other amino acids it would depend on what they are.

No, 5hpt doesn't seem to be losing effect but I'll just use it when necessary.

I'm also supplementing with: lysine, taurine, and valine (500 mg).

 

[Jimbo39]

The little cycle is showing that conversion of 10 formylTHF to THF can happen in three separate ways - ie the formyl group can be used in three separate reactions.

Boy, I got this all wrong.

 

[Jimbo39]

though for some amino acids there's only one codon which creates it.

So for methionine and tryptophan there's only one codon for creating these amino acids. That's bad because both play a critical role.

So the "A" on the end isn't indicative of it becoming a stop command, unless the first two nucleobases in the codon are TA or TG. Here's an amino acid wheel which shows the codons creating each amino acid or stop sequence (colored bits are non-adjacent codons which have the same outcome):

So TAA,TGA, AGT, and GAT are stop commands?

Serine (TGA) and aspergine(TGA) are susceptible to stop commands?

There is a stop command between tryptophan and cysteine and between serine and tyrosine. Does this make those amino acid susceptible as well?

I don't know what you mean about the "colored bits".

 

[Valentijn]

So TAA,TGA, AGT, and GAT are stop commands?

All except AGT, since that codes for Serine.

There is a stop command between tryptophan and cysteine and between serine and tyrosine. Does this make those amino acid susceptible as well?

I suppose any amino acid with two nucleobases in common with a stop codon are more likely to result in a premature termination. But that would probably be a lot of the amino acids, and maybe most of them.

 

[Valentijn]

So for methionine and tryptophan there's only one codon for creating these amino acids. That's bad because both play a critical role.

It's not necessarily bad. Though it does mean that if the third nucleobase in the codon changes, there will be a missense or nonsense mutation. Whereas many amino acids aren't affected with the third nucleobase changing.

 

[alicec]

Would supplementing with more than Freddd's recommended dosage (B2) lead to any kind of paradoxical reaction?

You seem to be overly concerned with "paradoxical" reactions.

Freddd found high doses of B2 seemed to drive the need for methylfolate but others have found the opposite - see this thread. Being able to produce sufficient FAD (ie ensuring that everything needed to convert riboflavin to the final active vitamin is in place) may reduce the need for methylfolate.

You'll just have to try things out and judge your own reactions.

 

[Jimbo39]

It's not necessarily bad. Though it does mean that if the third nucleobase in the codon changes, there will be a missense or nonsense mutation. Whereas many amino acids aren't affected with the third nucleobase changing.

I'm not sure if I understand all this but it seems that since methionine,for instance, only has one nucleobase (at the beginning of the sequence), whereas proline has 4 possible nucleobases, it would be more susceptible to mutation.

Ok, what I'm trying to say is, theres only one way to make methionine- GTA. Theres 4 possible ways to make proline- TCC,CCC,ACC,GCC. If one of the sequence of proline changes, there's still 3 other possible ways to make it.

 

[Jimbo39]

You seem to be overly concerned with "paradoxical" reactions.

You're right. I suppose some of it has to do with my Valium taper which has left me hyper-reactive.

Freddd found high doses of B2 seemed to drive the need for methylfolate but others have found the opposite - see this thread. Being able to produce sufficient FAD (ie ensuring that everything needed to convert riboflavin to the final active vitamin is in place) may reduce the need for methylfolate.

Yes, it's a very individual thing. I've read some of "B2, I love you" and there were conflicting reactions there as well.

On that note, I've been building up potassium and magnesium. I'm at 750 mg potassium, 400 magnesium, and 100 calcium. I've quit taking NAC and Yasklo's ALL IN ONE because it contains folic acid. To replace it (the minerals that is), I've started taking Seeking Health Trace Minerals Complex.

It's been about a week so I suppose I'm ready to start my B protocol.

 

[alicec]

Ok, what I'm trying to say is, theres only one way to make methionine- GTA. Theres 4 possible ways to make proline- TCC,CCC,ACC,GCC. If one of the sequence of proline changes, there's still 3 other possible ways to make it.

Why are you worrying about this? That is how translation of the genetic code has evolved over millions of years. It's maybe an interesting philosophical question from the point of view of what forces have driven this evolution, but otherwise, you are just tying yourself in knots over irrelevancies.

 

[Jimbo39]

I'm not worrying or tying myself in knots @alicec. I'm just kind of OCD in trying to understand stuff.

 

[Valentijn]

Ok, what I'm trying to say is, theres only one way to make methionine- GTA. Theres 4 possible ways to make proline- TCC,CCC,ACC,GCC. If one of the sequence of proline changes, there's still 3 other possible ways to make it.

Yes ... for a lot of amino acids, it won't matter if the third nucleobase in the codon changes. It'll still make the same amino acid, and is called a "synonymous" mutation.

Some of the silliest SNPs focused on by Yasko are synonymous mutations in exons. It's pretty well guaranteed that those SNPs won't have any impact, since their exact role is very well understood.

 

[Jimbo39]

Some of the silliest SNPs focused on by Yasko are synonymous mutations in exons. It's pretty well guaranteed that those SNPs won't have any impact, since their exact role is very well understood.

Thank you for giving me a basic understanding of genetics and how it relates to the production of enzymes. I can see how referencing one SNP without taking into account "synonymous mutations" would be meaningless.

I read about Prometheus. I can see how this would be an invaluable tool. It would be nice to know if you have a propensity to diabetes, for example, so that preventive measures can be taken.

Can you search for specific SNPs like MTHFR?

 

[Valentijn]

Can you search for specific SNPs like MTHFR?

It's been quite a while since I used it, but I think that should be pretty easy.

 

[Jimbo39]

@caledonia I read Start Low and Go Slow once again. Are you personally very sensitive to supplements? Do you think it may in part be due to your Benzo and SSRI withdrawal? I know benzo withdrawal can wreak havoc on your CNS.

You mentioned having high cortisol surges. Since you're sensitive to any adrenal support, how did you address it?

 

[caledonia]

@caledonia I read Start Low and Go Slow once again. Are you personally very sensitive to supplements? Do you think it may in part be due to your Benzo and SSRI withdrawal? I know benzo withdrawal can wreak havoc on your CNS.

You mentioned having high cortisol surges. Since you're sensitive to any adrenal support, how did you address it?

Ha - good question. Yes, I have a lot of weird sensitivities. I think it's more due to mercury and arsenic toxicity. This past year I stopped tolerated vitamin C and magnesium that I've taken for years, I believe due to the bad round of mercury chelation I did last year. Luckily I was able to find replacements after much trial and error.

For the adrenals, I replace the electrolytes which are being lost. I replace magnesium and potassium four times a day. I do sodium if I'm extra stressed and craving salt. If I'm even more stressed beyond that, I do small amounts of Dr. Wilson's Adrenal Rebuilder.

I've tried all of the traditional supplements like ACE and they're all too overstimulating. Dr. Wilson's has the hormones taken out.

Ultimately, it's going to take some years of chelation to get the adrenals completely fixed.