Methylation is the process of a molecule known as a 'methyl group', made up of 1 carbon and 3 hydrogens atoms, being applying in countless critical functions in your body such as: thinking, repairing DNA, turning genes on and off, fighting infections and getting rid of environmental toxins to name a few. Methylation occurs probably billions of times every second in every cell in your body!
DNA methylation is an epigenetic mechanism used by cells to control gene expression. A number of mechanisms exist to control gene expression but DNA methylation is a commonly used epigenetic signalling tool that can fix genes in the “off” position.
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 and adenosine through a reversible reaction. SAH is a potent inhibitor of methylation reactions. Efficient removal of adenosine and homocysteine is imperative to prevent accumulation of SAH. Homocysteine 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 homocysteine 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 homocysteine away from remethylation to methionine toward the 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.
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, ageing and exposures to environmental toxins. For example, lead can impair methylation via inhibition of the enzyme methylene-tetrahydrofolate reductase (MTHFR).