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Re: possible to precursor SAMe? » tendency

Posted by Larry Hoover on April 10, 2005, at 10:01:04

In reply to possible to precursor SAMe?, posted by tendency on April 5, 2005, at 11:08:34

> thought i read somewhere that you can precursor SAMe with TMG and B12. is this correct? thanks

Sorry for the delay in responding.....

There are two biochemical pathways which promote SAMe formation, and both exert that effect by recycling the SAMe "waste" product, homocysteine, back to methionine (the M in SAMe).

Here's how that works.

Pathway 1, the "standard" one in medical tunnel-think. A form of vitamin B12 (methylcobalamin), in combination with a form of folate (5-methyl-tetrahydrofolate) which must itself be synthesized from folic acid, and the appropriate enzyme, turns homocysteine into methionine. If there is no 5-MTF available (which depends on niacin for its formation from folic acid), the process will use SAMe for the methyl group transfer. As you can see, being folate deficient while taking B12 USES UP SAMe, RATHER THAN CREATING IT!

In any case, Path 1 uses B12, *and* folate, and indirectly, B3.

An alternative, and inducible (i.e. it will upregulate on supply of TMG, also known as betaine) pathway, we'll call Pathway 2. Some authors involve vitamin B12 and another form of folate, 5,10-methylenetetrahydrofolate....but it's unclear to me just how they fit in. Perhaps they recycle DMG to TMG?

The enzymatic reaction at betaine-homocysteine methyltransferase (BHMT) seems to involve only the presence of the two reactants, betaine and homocysteine, the cofactor zinc, (and probably one NAD+ (again, niacin-dependent)), yielding DMG and methionine. The zinc is actually a free atom here, so circulating zinc (as metallothionene-bound zinc) must be adequate. Choline is also an alternate to betaine, as choline is tetramethylglycine, one more methyl than betaine/trimethylglycine (TMG).

There's an interesting link between this enzyme and hyperhomocysteinemia combined with low taurine/cysteine levels.....

About 10% of the population have low activity of the vitamin B6-dependent enzyme cystathionine-ß-synthetase, which diverts homocysteine into what is called the trans-sulfuration pathway. The trans-sulfuration pathway produces cysteine and taurine. The betaine enzyme BHMT requires cysteine in its active site, so you need good cystathionine-ß-synthetase activity, or alternate means, to provide cysteine.

My recent interest in taurine, and the possibility of taurine deficiency, seems to be in accord with epidemiological evidence.

I react well to TMG, and I react well to taurine. These may be because of a genetic cystathionine-ß-synthetase defect.....Hmmmmm.

Anyway, I've rambled a long time....

You can learn a lot from these articles:
http://www.thorne.com/altmedrev/fulltext/meth1-4.html
http://www.gettingwell.com/drug_info/nmdrugprofiles/nutsupdrugs/bet_0331.shtml

In short, yes you can promote SAMe formation with B-12 and folic acid, or TMG and zinc, but if and only if B6 and B3 are already on the job.

Lar

 

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poster:Larry Hoover thread:480153
URL: http://www.dr-bob.org/babble/alter/20050323/msgs/482305.html