32 Overview over methionine metabolism: Implications in swine nutrition and health

Abstract Methionine (Met) can be referred to as a functional amino acid (AA) because besides serving as a building block for protein bio-syntheses, it also performs many other biochemical and physiological functions in swine body, simply due to its unique chemical structure and cellular metabolism. As a sulfur-containing AA (SAA), a Met molecule, as its name indicates, contains a methyl group covalently bonded to a sulfur atom via a thioether bond. In terms of its functions, first of all, Met is the initiator for virtually all protein bio-syntheses. Secondly, Met can be easily oxidized to a sulfoxide via a covalent modification, and the resulting Met sulfoxide can be readily reduced back to Met. In the case of protein-bound Met, both Met and cysteine (Cys) residues are most susceptible to oxidation and this nature can protect many proteins from oxidative damages. The biochemical metabolism of Met involves transmethylation, remethylation, transsulfuration, and transamination pathways. The initial step of transmethylation is generation of S-adenosylmethionine (SAM) which is an essential methyl donor in a myriad of metabolic events that include the methylation of DNA, RNA, proteins, phospholipids, and some small molecules. These various methylations dictate the replicational, transcriptional and translational fidelities, mismatch repair, chromatin modelling, epigenetic modification, imprinting, as well as detoxification of xenobiotics, which are all topics of great interest and importance in swine health and production performance. SAM is also a key metabolite to produce homocysteine which can be remethylated back to Met via the remethylation pathway (known as methyl cycle). The transsulfuration pathway firstly converts homocysteine to cystathionine via a condensation with serine, and then cystathionine is cleaved to Cys plus α-ketobutyrate and ammonia. Transsulfuration pathway is irreversible, and that is why Met is an indispensable AA whose deficiency cannot be remedied by Cys, whereas Cys is dispensable when more Met is provided. Because of this metabolic interconversion between Met and Cys in the body, these two are generally grouped together as SAA (Met + Cys) in swine nutrition practice. That said, when tissue Met concentration is too great, Met can be catabolized via its transamination pathway which is minor and SAM-independent. Met toxicity is mainly caused by methanethiol and H2S, two major toxic metabolites in the transamination pathway. Synthesized from Met, a myriad of proteins and peptides are involved in the functioning of immune system for maintaining animal health. For example, SAM is also a precursor for synthesis of polyamines which can enhance immune cell proliferation during an immune challenge. Cys and its derivatives (e.g., glutathione and taurine), in addition to their antioxidative capacity, can ameliorate inflammation during an immune response. In short, Met is a unique SAA that has numerous indispensable biological functions for supporting swine health and production performance.