Article Review Title: Methionine: An Essential Sulfur-Containing Amino Acid Name: Harriet Kaye A. Reyes, BSED Science 3A Institution: Isabela State University, Cauayan City Campus Abstract Methionine is the initiating amino acid in the synthesis of virtually all eukaryotic proteins. It is one of the most common sulfur-containing amino acid which is incorporated with proteins. Within proteins, many of the methionine residues are buried in the hydrophobic core, but some, which are exposed, are susceptible to oxidative damage. Methionine is crucial for both animal and human health as it understood to play a fundamental role in various metabolic processes and cellular functions. This article includes functions of methionine such as methylation processes that begins with its activation to S-adenosylmethionine, Detoxification and Antioxidant role, and its metabolic functions. These functions are essential in understanding the role of methionine as a versatile biomolecule. Methionine is essential for the normal growth and development of mammals. This essential role derives from the participation of this amino acid, or its derivatives, in several fundamental biologic processes, including protein synthesis and the numerous S adenosylmethionine. Along with its functions are the importance and applications to several to medical benefits, societal importance, and practical applications. Introduction Methionine is an essential sulfur-containing amino acid crucial for human and animal health. Being "essential" means the body cannot synthesize methionine and must acquire it through dietary intake. It plays a fundamental role in various metabolic processes and cellular functions. Methionine is obtained from animal-based dietary sources such as meat, fish, eggs, and dairy, as well as certain plant-based proteins like soybeans and lentils. It also studies the role in protein synthesis that serves as an initiating amino acid, which involves the process in Eukaryotic cells that begins in Methionine. This positioning is essential for the correct assembly of amino acids into functional proteins. During the last two decades, work in several laboratories has defined the potential pathways for methionine metabolism. Concurrently, other studies have established the existence of regulatory processes and have provided some insight into the individual mechanisms which may contribute to this metabolic modulation. Methionine plays an essential role in the immune system through its metabolites. In this regard, Blachier et, al. (2013) found that this amino acid directly influences the functioning of the immune system because of methionine catabolism leading to an increase in the production of glutathione, taurine, and other metabolites. This article provides an insight on the significance of methionine to its role in human and animal health, coupled with its medical, societal, and industrial significance. It will briefly summarize its functions, importance and applications to animal and human health. Structure Methionine is the most peculiar amino acid in terms of structure. Its molecular formula is C₅H₁₁NO₂S. The carbon atom at the center is an anchor to which all the functional groups of the molecule are attached. This central carbon is attached to an amino group (-NH₂), which defines methionine as an amino acid, and a carboxyl group (-COOH), which is needed for peptide bond formation during protein synthesis. Methionine is different from other amino acids because it contains a sulfurcontaining side chain (-CH₂-CH₂-S-CH₃), which is part of its metabolic processes and contributes to its special attributes. Figure 1. 2D Structure of Methionine The methionine amino acid structure is illustrated in figures 1. The methionine structure shows that this molecule has the regular amino acid backbone, which is basically: • • A central carbon atom. An amino group −NH2. • • The carboxyl group −COOH A unique sulfur-containing side chain (-CH₂-CH₂-S-CH₃), which sets it apart from other amino acids. Function of Methionine Protein Synthesis Methionine plays a critical role in protein synthesis, serving as the initiating amino acid during the translation process. In eukaryotic cells, the process begins with methionine being attached to a special initiator tRNA, known as tRNAᵐᵉᵗᵢ, which pairs with the start codon (AUG) on mRNA. This positioning is essential for the correct assembly of amino acids into functional proteins. As the key amino acid in protein synthesis, methionine is essential for translation across all life domains. Eukaryotes start synthesizing proteins from methionine and prokaryotic proteins based on N-formylmethionate. Why? Recognition of the start codon during translation is facilitated by the unique structure of methionine-specific tRNAᵐᵉᵗᵢ Figure 2. tRna in Protein Synthesis (Brosnan & Broslan, 2006; Tharp et al, 2021). Several pathways involved in protein biosynthesis must be controlled by methionine, which is essential for protein synthesis and regulation. Methionine deprivation has been shown to impact the S6K1 pathway, which is critical for protein synthesis regulation in avian myoblasts. Additionally, methionine has a dual role as initiation and precursor for S-methione (SAM), which is an essential methyl donor in several phenylation pathways, including those that affect DNA, RNA, and proteins (Lim et al. (2018)). Furthermore: Methionine's dual function as a protein and methyl group generator highlights its crucial role in cellular metabolism and gene expression regulation. Methylation Processes Methionine is essential for a number of methylation processes inside cellular metabolism because it can be converted into S-adenosylmethionine (SAM), the universal methyl donor in many biological activities. Methionine is essential for methylation, which regulates gene expression, DNA repair, and the synthesis of other biomolecules, in addition to protein synthesis. One of those necessary amino acids that your body cannot produce on its own is methionine, which you must obtain through diet. It functions as the precursor to S-adenosylmethionine, or Schematic presentation of DNA methylation. SAM, S-adenosyl methionine; SAH, S-adenosylhomocysteine; DNMTs, DNA methyltransferases; MBPs, methyl-binding proteins; HDACs, histone deacetylases. Created with BioRender.com SAM for short, which is crucial for many bodily functions. Do you realize that your body uses your DNA as a kind of script? SAM aids in DNA methylation, which is similar to modifying that script to ensure that everything is functioning properly. Additionally, it plays a role in the synthesis of neurotransmitters, which are the molecules that assist regulate your mood and include serotonin and dopamine. Do you know what phospholipids are? They are essential for maintaining the integrity of your cell membranes, and SAM is also involved in their production. SAM also plays a significant role in other processes that require the donation of a methyl group. This has an impact on hormone regulation, how your body handles fat, and even epigenetics. As strange as it may sound, methionine is the unsung hero that keeps our systems and cells functioning properly. Detoxification and Antioxidant Role Methionine is integral to the synthesis of glutathione, a tripeptide that serves as one of the body's most powerful antioxidants. Methionine (Met) is a sulfur-containing amino acid that is present in peptides and proteins. The most important common characteristic of Met residues in proteins is that they are subject to reversible oxidation and reduction, mediated either enzymatically or nonenzymatically (Kim et al. 2014). Met residues of proteins are especially susceptible to oxidation. Methionine neutralizes reactive oxygen species (ROS) and protects cells from oxidative damage and by some other biological oxidants. The susceptibility of proteinbound methionine to oxidation generally correlates with the surface exposure of a methionine residue. While surface-exposed Met residues are the most readily oxidized with negligible consequence for protein activity, Met residues buried within protein core, which are vital for function of a protein, are less prone to oxidation (Grune et al. 2013). The oxidation of protein-bound methionine to methionine sulfoxide (MetO) is considered as an undesirable and harmful consequence of oxidative stress, linked to age-related malfunctions (Stadtman et al. 2005; Ruiz et al. 2005; Pamplona and Barja 2006; Reeg and Grune 2015; Aledo 2021). Methionine also regenerates other antioxidants, such as vitamins C and E. Supports the detoxification of harmful substances in the liver and prevents the accumulation of toxic metabolites by enhancing liver function and metabolic detox pathways. Metabolic Functions In metabolic functions, it includes lipid metabolism which methionine supports the breakdown of lipids, helping to reduce fat deposits in the liver and promoting overall lipid balance. Methionine's role in the methionine cycle and methylation is associated with lipid regulation and reduced risks of non-alcoholic fatty liver disease (NAFLD) when in balance. Homocysteine regulation; through its conversion to cysteine and glutathione, methionine helps regulate homocysteine levels, which helps lower cardiovascular disease risks by reducing oxidative stress and inflammation. Energy production which methionine contributes to energy metabolism by participating in the synthesis of creatine, a compound critical for energy storage in muscles. The methionine – homocysteine cycle contains re-methylation and transculturation components. The enzyme S-adenosyl homocysteine hydrolase (SAH) contributes to methylation of DNA and RNA. Other abbreviations: CBS = cystathionine–b–synthase; MTR = 5-methylterathydrofolate-homocyteine methyltransferase; MTHFR = methyl tetrahydrofolate reductase; THF-tetrahydrofolate; MTHF = methyltetrahydrofolate. These diverse roles illustrate methionine’s importance not only in fundamental biological processes but also in maintaining cellular health and metabolic homeostasis. Importance Medical Importance/Benefits Methionine offers significant medical benefits, particularly for liver health, where it aids in detoxifying harmful substances and supports liver regeneration. Its derivative, S- adenosylmethionine (SAM), plays a vital role in neurochemical synthesis, facilitating the production of essential molecules like creatine and epinephrine. Additionally, methionine supplementation has shown promise in disease management, particularly in treating liver disorders and depression through SAM-related pathways, highlighting its therapeutic potential in maintaining and restoring overall health. Societal Importance Methionine holds profound societal importance, particularly in agriculture and human nutrition. In animal feed, it is an indispensable additive, enhancing livestock growth, improving meat quality, and boosting agricultural productivity by optimizing protein synthesis in animals. This use contributes to sustainable food production and economic efficiency in the farming sector. For human nutrition, methionine is crucial for maintaining dietary balance, especially for individuals following vegan or vegetarian diets, which often lack sulfur-containing amino acids. By preventing deficiencies, methionine supports overall health and nutritional adequacy. These applications highlight its pivotal role in supporting global food security and public health. Practical Applications Methionine has wide-ranging practical applications across industries due to its biochemical properties and versatility. As a dietary supplement, it addresses amino acid deficiencies, particularly in populations with dietary restrictions like vegans and vegetarians. Its role in detoxification supports liver health, particularly in conditions involving fatty liver and toxin overload. In biotechnology, methionine is an essential amino acid in microbial and cell culture media, optimizing cell growth and protein production for research and industrial use, such as in biopharmaceutical manufacturing. In pharmaceuticals, methionine is leveraged for its detoxifying and hepatoprotective properties, assisting in treatments for liver diseases and as part of formulations to support overall metabolic health. The cosmetic industry uses methionine in skin care products, promoting skin repair and collagen synthesis due to its sulfur content, which is vital for keratin production. These diverse applications underscore methionine’s critical role in advancing health, science, and industrial innovation. Conclusion Methionine is an amino acid which is essential for protein synthesis, methylation, and antioxidant protection. Its role in human and animal health, coupled with its medical, societal, and industrial significance, underscores as a versatile biomolecule. 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