The central theme of the methylation cycle is the conversion of homocysteine to methionine, an essential amino acid. The methylation cycle helps keep your homocysteine levels in check. As discussed in the earlier section, high homocysteine levels can lead to several health issues.
Here are the steps in the methylation cycle involving key enzymes and intermediates:
[1] Conversion of Serine to Glycine
- Enzyme: Serine Hydroxymethyltransferase (SHMT)
- Reaction: Serine + Tetrahydrofolate (THF) → Glycine + 5,10-Methylenetetrahydrofolate (5,10-MTHF)
[2] Conversion of 5,10-MTHF to 5-MTHF
- Enzyme: Methylenetetrahydrofolate Reductase (MTHFR)
- Reaction: 5,10-Methylenetetrahydrofolate (5,10-MTHF) → 5-Methyltetrahydrofolate (5-MTHF)
[3] Conversion of Homocysteine to Methionine
- Enzyme: Methionine Synthase (MTR)
- Reaction: Homocysteine + 5-Methyltetrahydrofolate (5-MTHF) → Methionine + Tetrahydrofolate (THF)
- Coenzyme: Methionine Synthase Reductase (MTRR) keeps MTR active
[4] Alternative Pathway for Homocysteine to Methionine
- Enzyme: Betaine-Homocysteine Methyltransferase (BHMT)
- Reaction: Homocysteine + Betaine → Methionine + Dimethylglycine
[5] Conversion of Methionine to SAM
- Enzyme: Methionine Adenosyltransferase (MAT)
- Reaction: Methionine + ATP → S-Adenosylmethionine (SAM)
[6] Methylation Reactions
- SAM as Methyl Donor: SAM donates a methyl group to various substrates (DNA, RNA, proteins, lipids) and becomes S-Adenosylhomocysteine (SAH).
[7] Conversion of SAH to Homocysteine
- Enzyme: S-Adenosylhomocysteine Hydrolase (SAHH)
- Reaction: S-Adenosylhomocysteine (SAH) → Homocysteine + Adenosine
[8] Transsulfuration Pathway (Alternative route for homocysteine) [we are here]
- Enzyme: Cystathionine Beta-Synthase (CBS)
- Reaction: Homocysteine + Serine → Cystathionine
- Subsequent Reaction: Cystathionine converts to cysteine and other metabolites.
The CBS gene produces the enzyme cystathionine beta-synthase. This enzyme uses Vitamin B6 (pyridoxine) to convert homocysteine and serine into cystathionine.
Additionally, through the transsulfuration process, cystathionine can be converted into taurine or glutathione. This process is crucial for making cysteine-containing amino acids, which are vital for protein structure, antioxidant activity, detoxification, and metabolic functions.
Importance of Healthy Homocysteine Levels
Appropriate homocysteine levels are essential because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis.Â
Additionally, elevated homocysteine is linked to other health issues such as cognitive decline, dementia, and certain birth flaws. Monitoring and managing homocysteine levels through diet, lifestyle changes, and, in some cases, medication, can be crucial for maintaining cardiovascular health and preventing related complications.