The nonessential amino acids serine and glycine play an important role in the human organism. They are necessary for the synthesis of proteins and peptides, nucleic acids and lipids, and for maintaining the antioxidant status of the cells. The organism’s need for these amino acids is met by their intake with food or by de novo synthesis intracellularly using glycolysis metabolites. Oncological transformation of cells causes increased proliferation and growth of tumor cells. To survive under stress, cancer cells need additional amounts of Ser and Gly, which leads to activation of their de novo synthesis. Metabolic reprogramming of cancer cells is recognized as a hallmark of tumor cells and plays a critical role in cell proliferation and survival. Amino acids are essential for cancer cells not only as nutrients but also as signaling molecules that can regulate gene expression and promote epigenetic modification. A key metabolic pathway influencing the epigenetic state of cancer cells is one-carbon metabolism, which includes the folate and methionine cycles. The interrelation of these cycles generates S-adenosylmethionine (SAM), a universal methyl donor required for DNA and histone methylation. The one-carbon units required for nucleotide synthesis are generated in a reaction catalyzed by cytosolic (SHMT1) and mitochondrial (SHMT2) serine hydroxymethyltransferases. Although SHMT1 and SHMT2 catalyze the same biochemical reactions, they play different biological roles in tumors. In most tumors, SHMT1 gene expression is decreased, while SHMT2 gene expression is increased. In various tumors, one-carbon units are recycled in Ser/Gly biosynthesis, which is accompanied by higher expression of the gene for the key enzyme of mitochondrial Gly synthesis, SHMT2. This enzyme catalyzes the reaction of formation of Gly and tetrahydrofolate-related one-carbon unit from Ser, supporting purine and thymidine synthesis and promoting tumor growth. The pro-oncogenic role of SHMT2 has been established, which is necessary for the survival of cancer cells and tumor growth in vivo with a poor prognosis for the patient. To maintain a high level of SHMT2 activity, increased expression of the SHMT2 gene is necessary, which is facilitated by complex regulatory mechanisms in tumor cells. SHMT2 expression can be regulated by methylation, acetylation, succinylation, phosphorylation, and lactylation. In addition, SHMT2 activity can be regulated by transcription factors, post-translational modification, or microRNA. SHMT2 depletion induces apoptosis by activating autophagy through metabolic reprogramming of tumor cells. The search for drugs that can target these enzymes is relevant for oncology. Therefore, studying the mechanisms of regulation of the activity of these key enzymes in cancer cells is of great importance. The review considers some mechanisms of regulation of the activity of these enzyme markers in cancer cells and the role of microRNA in modulating their activity.
L. A. Gavriliuk (Mon,) studied this question.