Methionine: Essential Roles in Physiology, Metabolism, and Health

Methionine

Methionine is an essential amino acid that plays many important roles in the human body. Chemically classified as a nonpolar, aliphatic amino acid, Met contains a α-amino group, a α-carboxylic acid group, and an L-configuration. Its IUPAC name is 2-amino-4-(methylamino)butanoic acid and it has the symbol Met or M. Met  is a sulphur-containing amino acid with the unique property of initiating protein synthesis in eukaryotes.

Biosynthesis and Dietary Sources

Humans cannot synthesize Met de novo and must obtain it through their diet. Plants, fungi and bacteria, Methionine are capable of synthesizing Met via the reverse transsulfuration pathway from aspartate and homocysteine. Major dietary sources of Met include meats, fish, eggs, garlic, lentils, yogurt, seeds and nuts. Met content varies with food type - chicken breast contains over 2 grams per 100 grams while almonds contain 0.8 grams per 100 grams. Cooking methods that involve high temperatures can destroy Met.

Physiological Functions

Methionine plays several critical physiological roles in the human body:

Protein synthesis: Met  acts as the initial amino acid in eukaryotic protein synthesis. Its unique properties make it capable of initiating translation. Almost all proteins contain Met residues at various positions along the polypeptide chain.

S-Adenosyl Met (SAMe): Met  is converted to SAMe, the second most common intracellular methyl group donor after S-adenosylhomocysteine. SAMe is required for methylation of tissues, neurotransmitters, hormones and more. It is involved in neurotransmitter synthesis, cell membrane integrity, cartilage formation and joint flexibility.

Antioxidant defense: Homocysteine produced from Met metabolism provides cysteine for glutathione synthesis. Glutathione is a major intracellular antioxidant that protects cells from oxidative damage.

Methylation reactions: SAMe donates its methyl group in hundreds of transmethylation reactions that produce important molecules like creatine, carnitine, phosphatidylcholine, melatonin and epinephrine. DNA, RNA, hormones and neurotransmitters are also methylated.

Detoxification: Met aids in detoxification and elimination of heavy metals and toxins through chelation and urine excretion. Its sulfur atoms can bind compounds like mercury, cadmium and lead for excretion.

Clinical Significance

Liver disease: Liver dysfunction impairs Met metabolism. Higher blood Methionine levels are seen in liver diseases like cirrhosis, fatty liver and hepatitis. Reduced methylation capacity contributes to effects like cognitive decline.

Cancer: Altered Met metabolism occurs in many cancers. Some tumor cells have a Met dependence for rapid growth. Use of Met restriction or antifolate drugs target this dependency.

Depression: Lower serum/red blood cell folate and vitamin B12 reduce SAMe synthesis from Met. SAMe deficiency increases depression risk and symptoms. Supplemental SAMe shows benefit as an antidepressant.

Aging: Age-related decline in methylation capacity may be due to lower SAMe levels from Methionine. Methylation affects DNA/histone maintenance and gene expression critical for longevity.

Genetic disorders: Inborn errors of Met metabolism include methyltetrahydrofolate reductase (MTHFR) deficiency and homocystinuria. These impair methylation reactions and elevate homocysteine levels.

Toxicity and Deficiency

Met is not considered toxic even at high doses in healthy individuals due to tight homeostatic control of sulfur amino acid metabolism. Symptoms of acute toxicity are extremely rare. Chronic Met excess may promote liver fat accumulation and NAFLD risks in susceptible people.

Met deficiency is rare but can develop from severe liver disease, malnutrition or very low protein/Met intake. Signs of deficiency include hair loss, nail changes, skin lesions, fatigue, weight loss and neuropsychiatric symptoms. Intravenous Met supplementation treats deficiency. The recommended daily intake for Met is set at 25 mg/kg body weight by authorities like the FDA.

Met serves as an indispensable dietary amino acid that is vital for protein synthesis, methylation reactions, antioxidant defenses and cellular detoxification in humans. Its essential roles in liver health, cancer biology, mental wellness and aging make Met a clinically important micronutrient. Further research continues to explore its therapeutic applications and links to important disease states.

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