Methionine

   Methionine is an essential amino acid that plays an important role in the methylation cycle. Methionine is obtained from dietary intake or through the remethylation of homocysteine.

    Dietary sources of methionine include eggs, fish, meat, Brazil nuts, and other plant seeds.

    Methionine is converted to the body’s primary methyl donor, S-adenosylmethionine (SAM). This conversion requires the enzyme methionine adenosyltransferase (MAT).

    Methionine elevations are most commonly caused by increased dietary intake. However, elevations can also be due to abnormalities within the methylation cycle itself, producing a passive elevation of methionine. Genetic SNPs for several methylation and transsulfuration enzymes, or a lack of necessary vitamin and mineral cofactors, can alter methionine metabolism. For example, a nutritional cofactor deficiency (magnesium/potassium), ATP depletion, or an SNP in the MAT enzyme can downregulate conversion to SAM and may lead to elevated methionine.

    Deficiency of vitamin B₆, a cofactor for the downstream enzyme responsible for transsulfuration of homocysteine, may result in excess remethylation of homocysteine ​​back to methionine, thereby increasing methionine.

    In addition, molybdenum is a cofactor in the degradation and catabolism of methionine, so molybdenum insufficiency may contribute to elevated methionine levels.

    Mild elevations in methionine do not cause serious adverse clinical effects. There is literature on CNS abnormalities seen with excessive elevations, but this is rare and more commonly seen with inborn errors of metabolism (MATI/III deficiency also known as Mudd disease).

    Low levels of essential amino acids may indicate a poor quality diet or poor digestion due to deficient digestive peptidase activity or pancreatic dysfunction. A deficiency of dietary methionine (low intake or malabsorption/maldigestion) may affect the methylation cycle, given its critical role. Increasing dietary sources of methionine, methionine supplementation, or supplementation with methylated products may mitigate the adverse impact.

    Because vitamins B₁₂ and folate are required to remethylate homocysteine ​​to methionine, the functional requirement for these cofactors may contribute to low methionine levels.

    Finally, vitamin B₃ deficiency has been associated with low levels of several amino acids.

LOW METHIONINE

• Decreased protein intake

• Protein malabsorption/ maldigestion

HIGH METHIONINE

• Increased dietary intake or supplementation (i.e. eggs, fish, meat, Brazil nuts, and other plant seeds)

• MAT SNP or lack of cofactors (ATP, Mg, K)

• Alcohol, oxidative stress affecting MAT