L-methionine belongs to the essential (vital) amino acids and cannot be produced by the human organism itself. Accordingly, an adequate dietary intake is of considerable importance. Methionine is an important source of sulfur in the human diet. It has a sulfur atom organically bound in the side chain between the CH2 and CH3 groups. The CH3-S-CH2-R- bond is also called thioether, where the R stands for the organic residue of the methionine molecule. In addition to methionine, cysteine is also one of the sulfur-containing amino acids, which reacts with another cysteine molecule to form a disulfide bridge – bond between two sulfur atoms, S-S bond – to form cystine. Uptake of the trace element sulfur occurs predominantly in the form of the S-containing methionine and cysteine. Since the side group of methionine carries neither a positive nor a negative charge, methionine is a neutral, nonpolar amino acid required for the endogenous synthesis of proteins and for this reason is called proteinogenic. In protein biosynthesis, methionine serves as a starter amino acid during translation. Protein biosynthesis or gene expression refers to the production of a protein or polypeptide and consists of the process of transcription – formation of messenger RNA from DNA – and translation – synthesis of a protein from messenger RNA. Translation, which takes place in the cytosol of cells, is downstream of transcription and involves transcription of messenger RNA (mRNA) with the participation of ribosomes and transfer RNA molecules (tRNA). The mRNA passes from the site of its synthesis, the nucleus, bound to proteins through the nuclear pores into the cytosol of the cells. The tRNA molecules provide the amino acids for protein biosynthesis and bind to the mRNA, while the ribosomes link the individual amino acids together to form a polypeptide by translocation (change of location) on the mRNA. The ribosomes are ultimately responsible for converting the base sequence of the mRNA into an amino acid sequence and thus into a protein. Protein formation from individual amino acids always begins at the start codon AUG of the mRNA. The three bases adenine-uracil-guanine – base triplet, codon – code specifically for methionine. According to this, the tRNA that starts protein biosynthesis (formation of new proteins) must be loaded with methionine in order to be able to bind with its base triplet UAC to the start codon of the mRNA under the influence of a ribosome. In a further step, a second tRNA loaded with an amino acid attaches to the following codon of the mRNA, also with the cooperation of the ribosome. Which amino acids are supplied by the tRNA molecules depends on the function of the protein to be synthesized, which the protein is to perform in the organism after its completion. Subsequently, the amino acid of the second tRNA, for example alanine, is enzymatically transferred to methionine by linking alanine and methionine by a peptide bond – formation of a dipeptide. By translocation of the ribosome on the mRNA and delivery of further amino acids with the help of tRNA molecules, the dipeptide is extended to a peptide chain. The polypeptide chain grows until one of the three stop codons of the mRNA appears. The amino acid-loaded tRNA molecules no longer bind, the synthesized protein is cleaved, and the mRNA detaches from the ribosome. The completed protein can now perform its function in the organism. Due to its importance as a starter amino acid in translation, methionine – represents the first N-terminal amino acid – of any protein.
Intestinal absorption
Methionine-rich dietary protein, such as egg, fish, liver, Brazil nut, and whole corn protein, is already broken down into smaller cleavage products, such as poly- and oligopeptides, in the stomach by the protein-cleaving enzyme pepsin. The site of main proteolysis (protein digestion) is the small intestine. There, the peptides come into contact with specific proteases (protein-cleaving enzymes), which release the individual amino acids that make up the poly- and oligopeptides. The proteases are produced in the pancreas and secreted into the small intestine as zymogens (inactive precursors). Shortly before the arrival of dietary protein, the zymogens are activated by enteropeptidases, calcium and the digestive enzyme trypsin.In the lumen of the small intestine, peptides are cleaved inside the molecule under the influence of the proteases chymotrypsin B and C, releasing methionine at the C-terminal end of the peptide chain. Methionine is now at the end of the protein, making it accessible for cleavage by zinc-dependent carboxypeptidase A. Carboxypeptidases are proteases that exclusively attack peptide bonds of the chain end and thus cleave certain amino acids from the carboxy or amino end of protein molecules. Accordingly, they are referred to as carboxy- or aminopeptidases. Methionine can be absorbed either as a free amino acid or bound to other amino acids, in the form of di- and tripeptides. In the free, unbound form, methionine is predominantly actively and electrogenically absorbed into the enterocytes (mucosa cells) of the small intestine in sodium cotransport. Driving this process is a cellward sodium gradient maintained by sodium/potassium ATPase. If methionine is still part of di- or tripeptides, these are transported into the enterocytes against a concentration gradient in proton cotransport. Intracellularly, the peptides are broken down by amino and dipeptidases into free amino acids, including methionine. Methionine leaves the enterocytes via various transport systems along the concentration gradient and is transported to the liver via the portal blood. Intestinal absorption of methionine is almost complete at nearly 100%. Nevertheless, there are differences in the rapidity of absorption. Essential amino acids, such as methionine, leucine, isoleucine, and valine, are absorbed much more rapidly than nonessential amino acids. The breakdown of dietary and endogenous proteins into low-molecular-weight cleavage products is not only important for peptide and amino acid uptake into enterocytes, but also serves to resolve the foreign nature of the protein molecule and to preclude immunological reactions.
