Lactate: a New Look at the Role of an Evolutionarily Ancient Metabolite

The review article presents a new look at the role of lactate in the human body. Lactate is known to have both positive and negative effects which depend on its concentration. Lactate concentrations up to 15 mM are optimal for the implementation of its positive effects, such as the involvement in tissue regeneration, preservation of neuronal integrity with a decrease in glucose levels, stimulation of adenosine catabolism and, as a result, a decrease in tumor immunosuppression, provision of a stem cell phenotype. Negative effects of lactate, which manifest themselves at concentrations above 15 mM, include the activation of hyaluronic acid catabolism, extracellular matrix (ECM) remodeling, stimulation of tumor exosome formation, provision of tumor cell proliferation, suppression of the immune response. It is lactate that is a precursor of many tricarboxylic acid (TCA) cycle metabolites in tumors, some of which are oncometabolites. It is possible that lactate hyperproduction by a tumor is not only a manifestation of tumor aggression, but also an adaptive response of cells of the tumor microenvironment, which thus regulates the activity of target genes, triggering a cascade of metabolic and physiological events.