Saturday, March 31, 2012

Buy the Natural Healing for Bipolar Disorder book by Eva Edelman and get to question the author

For a limited time only,  if you purchase a new Natural Healing for Bipolar Disorder from Borage Books, you will be able to set up a free 20 minute phone session (at your convenience).
Get your questions answered!  I look forward to talking with you.
                                                                                     Eva Edelman

Wednesday, March 28, 2012

Histadelia and Methylation. Part V-a: TransSulfuration Pathway

Homocysteine
Despite the notorious dangers of excess homocysteine,* normal levels are necessary to body chemistry, particularly the methylation cycle and the transsulfuration pathway. Homocysteine lies at the intersection of the two, serving as a precursor to methionine (which forms SAM), and also as the antecedent to cysteine, taurine, glutathione and sulfate.
* Chronically elevated homocysteine is infamous for its association with heart disease and may also play a role in memory impairment. It degrades collagen and elastin and damages the lining of blood and lymphatic vessels, via oxidative stress, inflammation, fibrin deposits, etc.  Similarly, it compromises the blood brain barrier.
During the methylation cycle, insufficient glutathione at the homocysteine-to-methionine step prevents methyl from linking to B12, and thereby impedes methionine formation.
Homocysteine  is instead diverted down the transsulfuration pathway to form glutathione.
This pathway transforms homocysteine into sulfur antioxidants and detox agents. And typically removes half the homocysteine from the methylation cycle.  But when it goes wrong, it produces toxic sulfur compounds. 
Here is an introduction to the chemistry:

Essentially:
 Homocysteine with the help of:
        vitamin B6 (as P5P), vitamin B3 (as NAD),
         magnesium, serine, selenium, molybdenum and oxygen
                       produces cysteine, glutathione, taurine and sulfate.
 Or, lacking required nutrients or energy, or with sulfur accumulation or dietary sulfur overload:
      Homocysteine forms cystine (instead of cysteine), excessive ammonia,  hydrogen sulfide and other toxic sulfur compounds.

Specifically (enzymes are in parenthesis):
1 Homocysteine  + B6  (as P5P*) + Mg   (via CBS)  yields Cysteine (+ AKG** + Ammonia).
2 Cysteine + serine + selenium + glutamate   yields  Glutathione.
3 Cysteine  + vitamin B3  (as NAD)   yields  Taurine.
4a Sulfite (from cysteine or food)  + molybdenum + B6 (P5P) + oxygen  (via SUOX***)   yields  Sulfate.
4b Without these nutrients, Sulfite produces toxic sulfur compounds.

* B6 metabolism to P5P is supported by AKG, B6, and magnesium. If there is difficulty forming P5P, it is often supplemented directly. 
** AKG (alpha-ketoglutaric acid) is a Kreb's energy cycle component. AKG also helps remove ammonia, and form P5P.
*** SUOX also influences the creation of glutathione.

Importance of Glutathione, Cysteine and Taurine
Glutathione is the body's premiere counter to oxidative stress, and is critical in encouraging homocysteine metabolism to methionine and SAM.
Cysteine is the precursor of glutathione, taurine and sulfate.
Taurine is a major inhibitory neurotransmitter, which often seems to stabilize both mood and neural activity (and also is critical in heart, eye, liver, and gall bladder function).

Next post: Sulfates, sulfites, and sulfur and phenol sensitivity.
For information on effects of histadelia on bipolar symptoms, see my book, Natural Healing for Bipolar Disorder.



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
 

Monday, March 12, 2012

Histadelia and Methylation. Part IV. What SAM does.

S-Adenosyl methionine (SAM) and Genetic Expression
1 By methylating DNA, regulates, usually suppressing, genetic expression, the process by which our genes cause RNA or specific proteins to be formed.
On the other hand, acetylation --by acetyl CoA, bolstered by folic acid-- typically promotes genetic expression.
So from moment to moment, the balance of SAM to folic acid at the chromatin strands, determines whether the chemical blue print encoded in the DNA will be used to form a new biomolecule, or will be suppressed.

2 Protects, repairs and stabilizes DNA.


Influence of SAM on dopamine, norepinephrine and serotonin activity
1 Functions as a natural reuptake inhibitor* for dopamine, norepinephrine and serotonin, increasing availability/activity of these neurotransmitters in the synapse.
Walsh explains that SAM inhibits reuptake epigenetically, by methylating (turning off) the neural membrane DNA which creates transporter proteins. If undermethylated, these transporters would remove neurotransmitters from the synapse, returning them to previous (pre-synaptic) neurons. Methylation by SAM, on the other hand, suppresses transporter creation, leading to an accumulation of dopamine, norepinephrine and serotonin in the synapse, thereby increasing neurotransmitter activity. (For more, see Nutrient Power by Dr. Walsh)

2 Influences tetrahydrobiopterin (BH4) synthesis of serotonin and dopamine: via methyl folate, which regulates BH4 production (click to enlarge).


3 Is used to recycle/inactivate norepinephrine, dopamine, epinephrine and serotonin.
  — With magnesium, forms COMT, which removes epinephrines and dopamine from the synapse. 
  — Regulates stress by metabolizing norepinephrine and epinephrine (adrenalin):  Methylates norepinephrine into epinephrine which, via COMT, is broken down into metanephrine.
  — With B5, metabolizes serotonin into melatonin (the hormone which triggers sleep).


SAM provides methyl to form proteins and lipids critical to mental function
1 Including melatonin, phosphatidyl choline, myelin, epinephrine, carnitine, Co-Q10and creatine. 
2 Also helps form  cholesterol, steroids, calmodulin (which modulates calcium use) and polyamines (from histamine). Inactivates estrogen by (forming a methyl estrogen).

SAM is important in immune function (which repercusses on mental function)
1  In turning off DNA replication, helps defend against viruses which use our DNA to replicate. 
2 Important to cell-mediated (non-antibody) immune function.
3 Helps flag and remove toxins.
4  Helps regulate the formation of sulphur molecules, such as cysteine, glutathione, sulphate, and taurine. These are major antioxidant and detox agents.
See next post, The Transsulfuration Cycle.
These diagrams provide a wider picture of cycle interactions (scroll down)

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

Monday, March 5, 2012

Histadelia and methylation. Part IIC: A Note on the Betaine Pathway

Betaine is trimethyl glycine. It is particular rich in beets and quinoa, and also found in spinach, broccoli and grains. The betaine-to-methionine pathway looks like this:

choline --via NAD (from B3) + choline-dehydrogenase + aldehyde-dehydrogenase-- yields betaine
* That is: trimethylethanolamine  --via NAD... -- goes to trimethylglycine

homocysteine + betaine   --via zinc + betaine-homocysteine-S-methyltransferase--  yields methionine + dimethyl glycine


Methionine proceeds, as in my previous post, to form SAM:
methionine   --via magnesium (or cobalt) + potassium + methionine adenosyl transferase--  yields SAM

See: diagram of the betaine pathway (enlarge)

Use of the folate vs. the betaine pathway
The betaine pathway is often not very efficient, especially when the folate/B12 to methionine pathway (previous posts) is being reasonably well-utilized

However, in people who drink alcohol regularly and in some others, the methyl-folate pathway may be too compromised to be effective, even with nutrient support. 
So you would then get homocysteine elevation, even when methyl is added to the system (e.g., with supplements of methyl B12, methionine and/or SAM).  The added methyl cannot help convert enough homocysteine back to SAM.
This situation is not common in histadelia, but can occur.

Therapeutic approaches (Walsh)
To restore methylation and better protect the heart:
1 Recycle HCY through the betaine pathway, above (and keep folate low to encourage this path).
2 Vitamin B6 and serine to convert homocysteine to sulfur antioxidants (coming up, post after next).
3 Address oxidative stress.

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

In the next post we will talk about what SAM does.