Wednesday, March 28, 2012

Histadelia and Methylation. Part V-a: TransSulfuration Pathway

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:

 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.

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