Coenzyme supplementation bypasses the body's need to synthesize the active forms of vitamin B-12 from cyanocobalamin.
Normal methionine metabolism is absolutely critical for folate-dependent transmethylation and transsulfuration. Abnormal metabolism of methionine can be found in both genders at any age. It is usually associated with genetic or nutritional deficiencies, aging and exposures to environmental toxins. For example, lead can impair methylation via inhibition of the enzyme methylene-tetrahydrofolate reductase (MTHFR).
Conditions associated with untreated, aberrant methionine metabolism include, but are not limited to:
Methionine is first enzymatically converted to S-adenosylmethionine (SAM), the principal methyl donor for methylation of DNA, RNA, protein, phospholipids, creatinine and neurotransmitters. S-adenosylhomocysteine (SAH) is generated as a product of transmethylation and is hydrolyzed to homocysteine (Hcy) and adenosine through a reversible reaction. SAH is a potent inhibitor of methylation reactions. Efficient removal of adenosine and Hcy is imperative to prevent accumulation of SAH. Hcy is normally removed or recycled by remethylation to methionine through a series of reactions that require 5-methyltetrahydrofolate, B12 and betaine to complete the normal methylation cycle. A low ratio of SAM to SAH is a sensitive indicator of under-methylation. Elevated plasma Hcy is an independent risk factor for cardiovascular disease (CVD). Recent research suggests that elevated SAH may be an even better predictor of risk for CVD.
Transsulfuration: Methionine > Homocysteine > Cysteine
The methionine transsulfuration pathway occurs primarily in the liver and diverts Hcy away from remethylation to methionine toward synthesis of the conditionally essential amino acid cysteine. Homocysteine in the presence of serine and B6 is enzymatically converted to cystathionine and ultimately cysteine. Cysteine is the rate-limiting amino acid in the biosynthesis of quintessential glutathione (GSH). GSH is pivotal in the regulation of intracellular redox homeostasis, oxidative stress, immune function, DNA synthesis and repair, apoptosis and detoxification of metals and chemicals.
The DDI Methylation profile evaluates the plasma levels of methionine, cysteine, SAM, SAH, Hcy and cystathionine, and provides the important "methylation index," a ratio of SAM to SAH. The test results can appropriately guide nutritional support to improve or normalize methionine metabolism and meliorate or prevent the potential adverse consequences associated with inadequate methylation and transsulfuration capacity.
Obviously, the two accepted dogma of vitamin B metabolism in the digestive tract don’t seem to correspond to reality: several compounds (vitamins B1, B2, B5, B8 and B9) supposedly absorbed by the small intestine may be assimilated by the colonocytes, while several compounds (vitamins B9 and B12) supposedly synthesized by colonic bacteria may actually be generated in the small intestine!