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The sulphurous α-amino acid L-methionine is essential to the human body and a constant level has to be maintained through nutrition. The main functions of L-methionine include the building of various protein molecules and the synthesis of the equally sulphurous amino acid L-cysteine. Well-known roles of cysteine include antioxidant defense, catalysis, protein structure, and redox sensing and regulation. As the metabolisation of excess L-methionine is connected to the formation of sulphuric acid, the kidneys can use L-methionine to acidify the urine, which enables the use of this essential amino acid for the treatment of certain conditions.

Methionine is metabolized mainly by the liver where it is converted to S-adenosylmethionine (SAMe) by the enzyme methionine adenosyltransferase. These reactions receive the general name of transmethylation reactions, and are catalyzed by specific methyltransferases (MTs). Over 200 proteins in the human genome have been identified as known or putative SAMe-dependent MTs.1 S-adenosylhomocysteine (SAH), an inhibitor of most MTs, is generated as a byproduct of all transmethylation reactions and is hydrolyzed to form homocysteine and adenosine by a reversible enzyme known as SAH hydrolase (AHCY). There are two fates for homocysteine: to be remethylated to regenerate methionine, or enter the transsulfuration pathway to be converted to cysteine and α-ketobutyrate. Although all mammalian cells synthesize SAMe, the liver is where the bulk of SAMe is generated as it is the organ where about 50% of all dietary methionine is metabolized. SAMe is mainly needed for methylation of a large variety of substrates (DNA, proteins, lipids and many other small molecules) and polyamine synthesis, so if the concentration of SAMe falls below a certain level or rises too much the normal function of the liver will be also affected. 

Methionine residues and cysteine residues of proteins are particularly sensitive to oxidation by ROS. However, unlike oxidation of other amino acid residues, the oxidation of these sulfur amino acids is reversible. Oxidation of methionine residues leads to the formation of both R- and Sstereoisomers of methionine sulfoxide (MetO) and most cells contain stereospecific methionine sulfoxide reductases (Msr’s) that catalyze the thioredoxin-dependent reduction of MetO residues back to methionine residues. g. The change in levels of MetO may reflect alterations in any one or more of many different mechanisms, including (i) an increase in the rate of ROS generation; (ii) a decrease in the antioxidant capacity; (iii) a decrease in proteolytic activities that preferentially degrade oxidized proteins; or (iv) a decrease in the ability to convert MetO residues back to Met residues, due either to a direct loss of Msr enzyme levels or indirectly to a loss in the availability of the reducing equivalents (thioredoxin, thioredoxin reductase, NADPH generation) involved. The importance of Msr activity is highlighted by the fact that aging is associated with a loss of Msr activities in a number of animal tissues, and mutations in mice leading to a decrease in the Msr levels lead to a decrease in the maximum life span, whereas overexpression of Msr leads to a dramatic increase in the maximum life span.