MTR and MTRR Genes: Methylation cycle and the need for Vitamin B12

The MTR (methionine synthase) gene and the MTRR (methionine synthase reductase) gene both code for enzymes that are involved in the conversion of homocysteine to methionine. They are essential players in the methylation cycle. This article explains where the MTR and MTRR genes fit within the methylation cycle. I'll show you how to check your 23andMe or AncestryDNA raw data for the MTR and MTRR SNPs, and then explain how to optimize your diet for these variants.

MTR & MTRR Gene: Methionine and Vitamin B12

Methionine is an essential amino acid, used in the production of proteins. It is literally the starting amino acid for every protein your body makes.
Methionine synthase (MTR) - image from Wikimedia Commons
Methionine synthase (MTR) - image from Wikimedia Commons
MTR (methionine synthase) and MTRR (methionine synthase reductase) code for two enzymes that work together in the methylation cycle.
  • The MTR gene works in the final step to regenerate homocysteine into methionine using methyl-B12 (methylcobalamin)
  • MTRR regenerates the methylcobalamin for MTR to use again.[ref]
Both are a vital part of the methylation cycle.

Methyl groups - in a nutshell:

Your body is made up of a bunch of organic molecules, a lot of which contain carbons bonded to hydrogen. Adding in a methyl group (one carbon plus three hydrogens) is like adding a building block onto the molecule. The methylation cycle is your body's way of cycling certain molecules to ensure that there are enough methyl groups (carbon plus three hydrogens) available for cellular processes. When it comes to the functioning of your cells, methyl groups are used in a bunch of ways.[ref] Examples of methylation reactions include:
  • synthesis of some of the nucleic acid (DNA) bases
  • turning off genes so that they aren't transcribed
  • converting serotonin into melatonin
  • methylating arsenic so that it can be excreted
  • regenerating methionine from homocysteine

Methylation in the right amount:

Goldilocks comes to mind here... You want to have the 'just right' amount of methylation reactions going on. Your cells work to keep this all in balance. For example, you need enough folate and methylcobalamin for the methionine synthase reaction to occur. Methyl folate is the source of the methyl group that methionine synthase uses for converting homocysteine to methionine. (Read more about your MTHFR genes and methyl folate) Not enough B12 or methyl folate? MTR won't convert as much homocysteine to methionine, leading to a buildup of homocysteine and limiting methionine. Too much homocysteine is associated with an increase in the risk of heart disease.[ref] The other side of the picture, though, is that there may be times that limiting methionine is helpful, such as in fighting the proliferation of cancer cells. Methotrexate, a chemotherapy drug, works by inhibiting the production of methyl folate, thus limiting methionine and DNA synthesis for cell growth.

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