Lactate metabolic pathway

The lactate metabolic pathway is a central metabolic route involving the interconversion of pyruvate and lactate by lactate dehydrogenase (LDH) and the transport of lactate across cell membranes by monocarboxylate transporters (MCTs) [PMID: 30104651]. While historically considered a metabolic byproduct, lactate is now understood to be a vital energy substrate and a signaling molecule that regulates gene expression and immune cell function [PMID: 31462518]. In many cancers, the pathway is upregulated via the Warburg effect, where cells preferentially produce lactate even under aerobic conditions to support rapid proliferation [PMID: 28854309]. This excessive lactate production creates an acidic microenvironment that facilitates tumor progression, metastasis, and immune evasion [PMID: 32661338]. Pharmacological targeting of this pathway primarily involves small-molecule inhibitors of LDH-A to reduce lactate production or MCT1/4 inhibitors to disrupt lactate transport [PMID: 33806106]. These interventions aim to induce metabolic stress and starve glycolytic tumors while potentially reversing the immunosuppressive effects of lactate accumulation. Clinical development of these inhibitors is ongoing, with a focus on combining them with standard-of-care therapies to overcome resistance. However, challenges remain regarding the systemic safety of inhibiting such a fundamental metabolic process, particularly in tissues like the heart and brain that utilize lactate for energy.

Other names

Lactate metabolismLactic acid metabolismAnaerobic glycolysis pathwayWarburg effect pathwayCori cycle

Inhibition of monocarboxylate transporters (MCT1/MCT4) to prevent lactate efflux and influx, and inhibition of lactate dehydrogenase (LDH) to prevent the interconversion of pyruvate and lactate, thereby disrupting glycolytic flux and cellular pH balance.