Monday, March 19, 2012

Histadelia and Methylation. Part IVB: SAM to HCY

1. In giving up its methyl to proteins and DNA, SAM becomes SAH.
2. SAH then releases adenosine and re-forms homocysteine. 
See diagram here.

SAH accumulation when adenosine is over-elevated
This latter reaction (2), however, is suppressed if adenosine and homocysteine are already excessive. Moreover, the reaction itself is reversible.
When SAH accumulates, it suppresses methylation (by inactivating methyltransferases).
This situation is usually due to severe oxidative stress, interfering with both methylation and glutathione availability.*

* Note: And is common in autistics. A study by Dr. S. Jill James, for instance, finds methionine, SAM and glutathione low, but excessive SAH, adenosine, homocysteine and oxidized glutathione. Sulfur antioxidants, including glutathione are excessively low, but excreted in the urine. Severe oxidative stress (compounded by metal metabolism dysfunction) interferes with methionine formation via methyl B12, thus compromising methylation. Further discussion of autism chemistry here.

Histadelic bipolar treatment (Walsh) 
(In presence of severe oxidative stress, creating SAH and perhaps some HCY accumulation.)
1 Supply glutathione to create homocysteine from SAH, and to attach methyl to B12 so it will convert HCY to methionine. Or, methyl-B12 may need to be provided directly.
2 Address any factors worsening oxidative stress, such as metal metabolism dysfunction.

On the other hand, if the cycle proceeds normally, we get:
SAM methylation reactions  --via methyl transferase--   yield SAH
SAH  --via  SAH hydrolase--- yields adenosine + homocysteine

At homocysteine we come to diverging paths
1 Homocysteine may continue within the methylation cycle.
2 However, when more glutathione is needed to support the methyl B12/ methionine synthase step, which turns homocysteine into methionine,
homocysteine is diverted down the transsulfuration pathyway to create more glutathione.

See Dr. Deth's discussion of this choice point here:

Our next post, will explain more about the Trans-Sulfuration Pathway, which, when functioning well, creates critical sulfur antioxidants, and ultimately transforms or eliminates problematic sulfur compounds and other toxins.

Reminder: This information is presented for educational purposes only, and is not intended as diagnosis or treatment recommendations for the individual. Even within the histadelic subgroup, each person's biochemical requirements tend to be unique. So if you need treatment for depression, mania, bipolar, or any other medical condition, please consult a knowledgeable physician. 

For info on the role of histadelia in bipolar disorder, see my book, Natural Healing for Bipolar Disorder

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