What Is Methionine? Other Names: D-Methionine, DL-Methionine, L-Méthionine

What is Methionine?

This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. Methionine is an essential sulfur-containing amino acid that plays a critical role in various biological processes. It is indispensable for protein synthesis and serves as a primary methyl donor in numerous transmethylation reactions, which are crucial for producing metabolites such as creatine, phosphatidylcholine (PC), and methylated DNA1.  Other names include: D-Methionine, DL-Methionine, DL Methionine, DL-Méthionine, L-2-amino-4-(methylthio)butyric acid, L-Methionine, L-Méthionine, Méthionine, Metionina.

Biological Functions

Methionine is involved in several key physiological functions:

Protein Synthesis: Methionine is a building block for proteins. In neonatal piglets, it has been observed that only one-third of methionine flux is incorporated into protein synthesis, while the remaining two-thirds are used in transmethylation reactions1.

Methyl Donor: Methionine is the primary methyl donor for over 50 transmethylation reactions, which are essential for the synthesis of various metabolites, including creatine and PC1.

Antioxidant Properties: Methionine has antioxidative activity, which helps in reducing oxidative stress and inflammation. It has been shown to inhibit the accumulation of 4-hydroxy-2-nonenal (HNE), a biomarker for oxidative stress, thereby suppressing inflammation9.

Dietary Requirements and Effects

The dietary requirement for methionine varies depending on the physiological state and dietary composition:

In Neonatal Piglets: Higher dietary methionine is required to maximize the synthesis of creatine compared to protein synthesis, indicating that non-protein demands should be considered when determining methionine requirements1.

In Adult Men: Supplementation with betaine, a methyl donor, increases the dietary requirement for methionine due to enhanced transmethylation and methionine oxidation rates2.

In Broilers: Methionine is the first limiting amino acid in poultry diets. Methionine deficiency can lead to liver and kidney injury, oxidative stress, and immunosuppression in the ileum3.

Health Implications

Methionine intake has significant health implications:

Liver and Kidney Health: Methionine deficiency can cause liver and kidney damage, as observed in broilers fed a methionine-deficient diet3.

Fat Metabolism: Methionine restriction promotes fat browning and reduces hepatic lipid accumulation, which is associated with improved thyroid function4.

Carcinogenesis: Methionine supplementation has been shown to promote intestinal carcinogenesis in rats, indicating that excessive methionine intake may have adverse effects5.

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Uses of Methionine

Protein Synthesis

Methionine is indispensable for synthesizing proteins, which are crucial for growth and repair in the body2.

Methylation Reactions

Methionine is the primary methyl donor for over 50 transmethylation reactions, producing important metabolites such as creatine, phosphatidylcholine (PC), and methylated DNA2. These reactions are vital for various biological processes, including DNA methylation and cellular function.

Antioxidant Activity

Methionine has significant antioxidant properties. It can modify tissue sensitivity against oxidizing agents and protect against oxidative stress. Studies have shown that methionine supplementation can influence levels of antioxidants like Vitamin C and E, as well as other serum parameters such as peroxynitrite, zinc, copper, albumin, and selenium1.

Growth and Development

In animal studies, methionine has been shown to be crucial for growth. For instance, in neonatal piglets, methionine is required not only for protein synthesis but also for the synthesis of key transmethylated products like creatine and PC, which are essential for growth and development2.

Detoxification

Methionine can help in detoxification processes. Excess methionine intake can lead to hyperhomocysteinemia, a condition characterized by high levels of homocysteine in the blood, which is toxic. However, methionine’s effects can be mitigated by betaine supplementation, which helps lower plasma homocysteine levels and reduce associated toxic effects3.

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Adverse Effects of Methionine

Liver and Kidney Health

Methionine Deficiency: A methionine-deficient diet can lead to liver and kidney injury, characterized by decreased antioxidant capacity and immunosuppression in the ileum1.

Methionine Excess: Excessive methionine intake can cause hyperhomocysteinemia, which is associated with cardiovascular issues and increased oxidative stress3 5.

Genotoxicity

Chromosomal and DNA Damage: High methionine levels can induce chromosomal damage and DNA damage in peripheral blood, although it does not affect the liver and heart tissues similarly2.

Cardiovascular Health

Hyperhomocysteinemia: Excess methionine can lead to elevated homocysteine levels, which are linked to cardiovascular diseases. This condition can be mitigated by betaine supplementation3 5.

Histopathological Changes: Methionine-rich diets can cause deleterious effects on cardiac tissues, although aortic tissues may remain unaffected5.

Oxidative Stress and Platelet Function

Oxidative Stress: Both acute and chronic methionine administration can increase reactive oxygen species (ROS) levels and reduce antioxidant enzyme activities, leading to oxidative stress and potential platelet dysfunction4.

Platelet Dysfunction: Changes in adenine nucleotide hydrolysis and redox status in platelets and serum can be associated with platelet dysfunction in hypermethioninemia4.

Reproductive Health

Ovarian Health: High doses of methionine can decrease the number of primordial ovarian follicles, potentially affecting fertility6.

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How has Methionine Improved Patient Outcomes?

Major Depressive Disorder

S-adenosyl methionine (SAMe), a derivative of methionine, was tested in patients with major depressive disorder (MDD). SAMe significantly increased plasma levels of SAMe and S-adenosyl homocysteine (SAH) without causing toxic effects, suggesting it is safe for use in MDD patients1.

Metabolic Health

Methionine and cysteine restriction in overweight or obese women showed beneficial effects on cardiometabolic risk factors, including increased serum fibroblast growth factor 21 (FGF21) and changes in adipose tissue gene expression, indicating improved metabolic health2.

In obese adults with metabolic syndrome, methionine restriction increased fat oxidation and reduced intrahepatic lipid content, independent of weight loss and improved insulin sensitivity3.

Cancer Treatment

Recombinant methioninase (rMETase), which depletes methionine, was effective in overcoming resistance to gemcitabine in pancreatic cancer and reducing tumor growth in Ewing’s sarcoma in patient-derived orthotopic xenograft (PDOX) models4 7.

Preoperative methionine-depleting parenteral nutrition combined with chemotherapy showed a suppressive effect on gastric cancer cell proliferation, suggesting a potential therapeutic strategy8.

AIDS-Associated Myelopathy

L-methionine treatment in AIDS-associated myelopathy (AM) showed a nonsignificant improvement in central conduction time (CCT) and increased cerebrospinal fluid (CSF) SAM levels, indicating some potential benefits without significant adverse effects5.

Fibromyalgia

Intravenous SAMe showed a tendency towards improvement in subjective pain perception and overall well-being in fibromyalgia patients, although no significant differences were observed in primary outcomes6.

Sperm Quality in Aging Mice

Methionine restriction improved sperm quality, reduced testicular inflammation and oxidative stress, and altered DNA and RNA methylation in aging mice, suggesting potential benefits for reproductive health10.

Fat Browning and Hepatic Lipid Accumulation

Methionine restriction promoted fat browning, reduced hepatic lipid accumulation, and improved thyroid function in mice, indicating potential benefits for metabolic health9.

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Methionine Mechanisms of Action

Antioxidant Activity

Methionine exhibits significant antioxidant properties. It condenses with ATP to form S-adenosylmethionine (SAM), which acts as a methylation donor in various biological pathways, helping to protect tissues against oxidative stress5. Methionine supplementation has been shown to reduce oxidative stress markers such as 4-hydroxy-2-nonenal (HNE) and increase antioxidant defenses like glutathione S-transferase (GST)2.

Anti-inflammatory Effects

Methionine can suppress inflammation by inhibiting the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. This is achieved through the up-regulation of inhibitory κBα and the depression of phosphoinositide 3 kinase/protein kinase B pathways. Additionally, methionine increases the levels of anti-inflammatory cytokines like interleukin-10 (IL-10)2.

Regulation of Lipid Metabolism

Methionine restriction in diets has been shown to promote fat browning and reduce hepatic lipid accumulation. This is associated with improved thyroid function, increased heat production, and enhanced fat catabolism1. SAM, a derivative of methionine, can also counteract estrogen-induced bile secretion impairment, thereby preventing cholesterol supersaturation in the gallbladder3.

Enzyme Regulation

Methionine availability regulates the activity of glycine N-methyltransferase (GNMT), which in turn modulates the levels of SAM and S-adenosylhomocysteine (SAH). This regulation is dose-dependent and tissue-specific, with significant effects observed in the liver and, to a lesser extent, the kidney4.

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Common Complaints Associated with Methionine Use

Liver and Kidney Injury: Methionine deficiency (MD) can lead to significant liver and kidney damage. This is evidenced by morphological signs of injury, decreased levels of liver enzymes (aspartate aminotransferase and alanine aminotransferase), and markers of kidney function (creatinine and uric acid) in broilers on a methionine-deficient diet1.

Oxidative Stress: Methionine deficiency is linked to increased oxidative stress. This is indicated by decreased superoxide dismutase activity and increased malondialdehyde content, which are markers of oxidative damage1.

Immunosuppression: Methionine deficiency can suppress the immune system. This is shown by decreased numbers of T and B lymphocytes and reduced expression of essential cytokines (IL-2, IL-6, LITAF, and IFN-γ) in the ileum, which is part of the gut-liver-kidney axis1.

Hepatic Lipid Accumulation: While methionine restriction (MRD) can have some beneficial effects, such as promoting fat browning and reducing hepatic lipid accumulation, it can also lead to changes in liver function and structure. This includes reduced hepatic and plasma lipid levels and changes in the liver’s fatty infiltration area2.

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