MTR (methionine synthase) combines folate, methyl B12 and homocysteine into methionine. Variants in MTR are upregulations, so it tries to go faster. MTRR attaches a methyl group to B12, and variants here will slow the process. When both MTR and MTRR exist, dysfunction can occur. Variants in MTR are upregulations, so it tries to go faster.
Nitric oxide (NO) inhibits MTR and B12 from acting as a coenzyme for methionine synthase. and thus inhibits the cycle. Those with MTHFR and methylation defects already have limited MTR enzyme function. A deficiency in B12, zinc, folate and selenium, oxidative stress (especially from high fructose corn syrup and refined sugar) alcohol, candida, the birth control pill, lead, mercury and cadmium (non-organic foods) all shut down methionine synthase. Those with immune dysfunction, chronic fatigue syndrome, chemical sensitivity, Lyme’s Disease, fibromyalgia tend to have higher NO levels.