MOLECULE

Methionine

Methionine, l-methionine abbreviated Met or M, is one of 9 essential amino acids (meaning the body cannot synthesize it; it must be obtained from the diet) required for protein synthesis and for normal growth and development of humans, other mammals, and avian species. It is a white crystalline powder with a mild acidic and sulfurous taste. It is an intermediate in transmethylation reactions, serving as the major methyl group donor for DNA and RNA intermediates. Methionine is a methyl acceptor for 5-methyltetrahydrofolate-homocysteine methyltransferase (methionine synthase), the only reaction that allows for the recycling of this form of folate and is also a methyl acceptor for the catabolism of betaine. Methionine is the metabolic precursor for cysteine where the sulfur atom from methionine is transferred to cysteine (PMID: 16702340). Methionine is an amino acid found in cannabis plants (PMID: 6991645). Methionine is one of 4 sulfur amino acids (SAA) that also include cysteine, taurine and homocysteine (with the latter two not incorporated into proteins). The WHO recommends that healthy adults consume 13 mg/kg per 24 h of normal SAA and roughly double this amount in artificial nutrition regimens. However, in disease or after trauma, SAA requirements may vary. SAA supplementation exceeding 2-3 times the minimum recommended daily intake can be considered safe except in specific cases of congenital enzyme deficiency, prematurity, or diminished liver function where hypermethioninemia or hyperhomocysteinemia may occur. Apart from acetaminophen poisoning, the usefulness of SAA supplementation is not yet established (PMID: 16702341). When present in high levels, methionine can act as an atherogen which is a compound that causes atherosclerosis and cardiovascular disease. Methionine is a precursor of homocysteine. Acute doses of methionine can lead to acute increases in plasma homocysteine, which has been used as an indicator of susceptibility to cardiovascular disease. Longer-term studies in adults have indicated that methionine intakes higher than 5 times the normal amount resulted in elevated homocysteine levels. Rodents fed high levels of methionine developed atherosclerotic plaques independently of homocysteine levels (PMID: 26647293). A similar study in Finnish men showed that high dietary methionine increased the risk of acute coronary events in middle-aged men (PMID: 16487911). These effects of methionine on homocysteine and vascular function are moderated by supplements of vitamins B-6, B-12, C, and folic acid (PMID: 16702346). Methionine is also a metabotoxin, which is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of methionine are associated with at least ten inborn errors of metabolism, including cystathionine beta-synthase deficiency, glycine N-methyltransferase deficiency, homocystinuria, tyrosinemia, galactosemia, homocystinuria-megaloblastic anemia due to defects in cobalamin metabolism, methionine adenosyltransferase deficiency, methylenetetrahydrofolate reductase deficiency, and S-adenosylhomocysteine (SAH) hydrolase deficiency (PMID: 16702350). Chronically elevated levels of methionine in infants can lead to intellectual disability and other neurological problems, delays in motor skills, sluggishness, muscle weakness, and liver problems. Many individuals with these metabolic disorders tend to develop cardiovascular disease later in life. Methionine is known to exacerbate psychopathological symptoms in schizophrenic patients, with no effects on healthy subjects.