Monday, February 7, 2011

EGCG, DYRK and Folate ie. green tea, increased gene and a B vitamin... Kinda.....

I took a minibreak from DYRK1A etc. But it is time to think about it again. Andi commented below about green tea and folate and I was getting to that but it involves another pathway.........Methylation.

Methylation is a very important basic process in the body. In the late 1990's Neal and his buddies with DS sent their blood to a researcher named Dr. Jill James. She discovered that the methylation pathway is disturbed in DS (and in us Moms) because some of the enzymes in the pathway are overexpressed. It is easier to look at a diagram than just to write about it.

Here is an overview of the Methylation Pathway. We are going to talk about the 2 things in red. In the middle of the diagram is CBS (cystathione beta synthase). This enzyme is triplicated on the 21st chromosome which presumably pulls that pathway down.
The second scratchy red is 5-CH3 THF - which is methyl tetrahyrdrofolate.
Have you have heard of folic acid? It is added to every cereal. "Fortified with Folic Acid".

There is a very knowledgable website called Super Down Syndrome that has a terrific explanation about many topics. But one is an explanation about folic acid versus folinic acid.
"...medical professionals still haven’t figured out that folic acid is not the same as the naturally occurring vitamin folate.

Folic acid is a single type of molecule, crystallized in 1943 by a scientist working for the patent medicine company Lederle Laboratories, then a subsidiary of American Cyanamid Corporation. Folic acid is the fully oxidized form of naturally occurring folates, which are found in leafy and green vegetables......

Folate was originally isolated from brewer’s yeast and spinach in the 1930s. Once isolated and exposed to air it becomes unstable and breaks down, and is generally no longer useful in nutrition. But a small amount of natural folate can be transformed by oxidation (a natural process) into folic acid, a much more stable form with a very long shelf life.
While human and animal cells cannot use the folic acid molecule itself in their normal metabolic processes, human cells (principally the liver) can transform folic acid back into many of its metabolically useful folate forms. That’s why folic acid—despite not being found in food—can do so much nutritional good, the best-known example being the prevention of birth defects including spina bifida, cleft lip, and cleft palate."
But what if your population cannot utilize folic acid? It is necessary to supplement with the more active form folinic acid which translates to 5-methyl tetrahydrofolate. Sound familiar? It is the folate in the cycle.

 Neal and I for that matter supplement with Folinic acid.

OK here comes the complication from green tea extract and folates. Green tea reduces an enzyme (DHFR) [orange] that converts folic acid tetrahydrofolate in one direction - here is another diagram:
But I now think that the DYRK1A is sufficiently dangerous that it is worth turning it down and then supplementing with a good form of folate. It is important to add B12 (green) as well. You didn't think this was going to be easy did you? The medical profession has thrown their collective hands up for years saying Down syndrome is too complicated to treat. They continue to say there are too many things wrong. True enough. But I think we can unpeel this syndrome like an onion. Don't get discouraged that there is another layer. Be prepared there are more layers to come.
We will look more closely at these pathways because there are more complications than we have discussed today.

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