From the FDA Drug Label
12.1 Mechanism of Action Betaine Anhydrous for Oral Solution acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. The relationship between Trimethylglycine (TMG) and the methionine-homocysteine pathway is that TMG acts as a methyl group donor in the remethylation of homocysteine to methionine. This process is crucial in patients with homocystinuria, as it helps to lower plasma homocysteine concentrations 1.
- Key points:
- TMG is a methyl group donor
- Remethylation of homocysteine to methionine
- Important in patients with homocystinuria
- Lowers plasma homocysteine concentrations 1
From the Research
Trimethylglycine (TMG) plays a crucial role in the methionine-homocysteine pathway by serving as a methyl donor for the remethylation of homocysteine back to methionine, a reaction catalyzed by the enzyme betaine-homocysteine methyltransferase (BHMT). The methionine-homocysteine pathway is a complex biochemical process that involves the conversion between the amino acids methionine and homocysteine. In this pathway, methionine is first converted to S-adenosylmethionine (SAM), which serves as a universal methyl donor for numerous biochemical reactions. After donating its methyl group, SAM becomes S-adenosylhomocysteine (SAH), which is then hydrolyzed to homocysteine. Homocysteine can either be remethylated back to methionine or converted to cysteine through the transsulfuration pathway.
Key points about the methionine-homocysteine pathway and the role of TMG include:
- TMG supplementation can help lower elevated homocysteine levels, which is important because high homocysteine is associated with cardiovascular disease, cognitive decline, and other health issues 2.
- The pathway requires adequate B vitamins, particularly B12, B6, and folate, which serve as cofactors for various enzymes involved in homocysteine metabolism 3.
- Disruptions in this pathway can lead to hyperhomocysteinemia and potentially contribute to various pathological conditions, such as thrombovascular diseases 4.
- The clinical consequences of disruption of these pathways can be apparent in rare inborn errors of metabolism that cause homocystinuria, as well as in "hyperhomocysteinemia" - a lesser metabolic impairment that may result from genetic variations, acquired pathology, toxicity, and nutritional inadequacy 4.
In terms of the relationship between TMG and the methionine-homocysteine pathway, TMG supplementation can be an effective way to support the remethylation of homocysteine back to methionine, particularly in individuals with elevated homocysteine levels or those who are at risk for hyperhomocysteinemia. This is supported by studies such as the one published in The Journal of Nutrition in 1996, which found that long-term betaine supplementation caused a substantial lowering of plasma homocysteine in patients with pyridoxine-resistant homocystinuria and gross hyperhomocysteinemia due to deficiency of cystathionine beta-synthase activity 2.