Posttranslational Regulation of Mammalian Sulfur Amino Acid Metabolism

Metabolism of the mammalian proteinogenic sulfur amino acids methionine and cysteine includes the methionine cycle and reverse transsulfuration pathway, establishing many connections with other important metabolic routes. The main source of these amino acids is the diet, which also provides B vitamins required as cofactors for several enzymes of the metabolism of these amino acids. While methionine is considered an essential amino acid, cysteine can be produced from methionine in a series of reactions that also generate homocysteine, a non-proteinogenic amino acid linking reverse transsulfuration with the methionine and folate cycles. These pathways produce key metabolites that participate in synthesizing a large variety of compounds and important regulatory processes (e.g., epigenetic methylations). The impairment of sulfur amino acid metabolism manifests in many pathological processes, mostly correlated with oxidative stress and alterations in glutathione levels that also depend on this part of the cellular metabolism. This review analyzes the current knowledge on the posttranslational regulation of mammalian sulfur amino acid metabolism, highlighting the large number of modification sites reported through high-throughput studies and the surprisingly limited knowledge of their functional impact.