Methionine synthase and the methyl cycle

Methylcobalamin is the working partner for methionine synthase, the enzyme that hands a methyl group from folate to homocysteine and makes methionine. Methionine becomes SAM, the body's universal methyl donor, which methylates DNA, myelin proteins, neurotransmitters and hundreds of other targets. With B12 short, that handover stalls: homocysteine climbs, folate is stuck in a form the cell cannot use, and methylation slows everywhere at once. This single stalled step explains why a shortage shows up in blood, nerves and mood together.