So I’m back with part 3 of our Homocysteine blog series. In part 2, I covered the primary recycling pathway of Homocysteine in the body which utilizes MTHFR, MTR, Methylation and Zinc to produce Methionine and THF.
Because Methylation is such a critical process in the body, there is a backup process for recycling Homocysteine that occurs in the liver and kidneys. This backup process utilizes an enzyme called BHMT.
BHMT utilizes Betaine (trimethylglycine from Choline) and Zinc to catalyze the reaction. Betaine is the methyl donor transferring a methyl group to Methionine. Out of the reaction Methionine and DMG (Dimethylglycine) are produced. The Methionine is once again used to produce SAM and DMG is used to produce Sarcosine.
Low levels of Zinc, Betaine and/or Choline can slow this reaction. There are BHMT SNPs which can reduce this enzyme’s function. Glucocorticoids can promote the activation of this enzyme. Elevations of SAM and DMG will inhibit BHMT activity.
This is a great backup system to support Methylation in the liver and kidney, but this isn’t happening in the rest of the body. Upregulation of this pathway because of blocks in the primary pathway can divert Choline and Betaine away from other important actions to support this pathway.
Betaine is produced from Choline or consumed in the diet. Natural foods like beets and spinach are rich in Betaine. Grains are rich in Betaine as well, but not a great source due to their inflammatory effects. So, if increased use Betaine via BHMT pathway and reduced intake in diet, than the body will synthesize it from choline. Heavy conversion of Choline to Betaine can create challenges as well.
Choline can come directly from foods like eggs or be synthesized by the enzyme PEMT. Choline is used to make Phosphatidyl choline which is used to make neurotransmitters, and cell membranes. The greatest amount of Choline is stored in our cell membrane as part of the membrane structure. In times of Choline and/or Betaine deficiencies, cell walls can be broken down to use as a source of Choline. The breakdown of cell membranes increases cellular inflammation and cell death. Reduced Choline levels are associated with cardiovascular disease, cerebrovascular disease, cognitive decline, fatty liver and cancer.