Lactate dehydrogenase 5 (LDH-5)

Lactate dehydrogenase 5 (LDH-5) is a tetrameric enzyme composed of four A subunits (LDHA) that plays a critical role in cellular metabolism by catalyzing the reversible conversion of pyruvate to lactate while regenerating NAD+ from NADH (UniProt P00338). Under anaerobic conditions or in rapidly proliferating cells, LDH-5 is the primary isoenzyme responsible for maintaining glycolytic flux, which is essential for ATP production when oxidative phosphorylation is insufficient or bypassed (PubMed 21169515). In the context of oncology, LDH-5 is frequently overexpressed in various solid tumors, a phenomenon known as the Warburg effect, where it supports the metabolic demands of cancer cells and contributes to an acidic microenvironment that promotes invasion and immune evasion (PubMed 26851588). Consequently, LDH-5 has emerged as a significant therapeutic target, with several small-molecule inhibitors being developed to disrupt tumor metabolism and induce cell death. Clinical interest also extends to its use as a prognostic biomarker, as high levels of LDH-5 in serum or tumor tissue are often associated with poor patient outcomes and resistance to conventional therapies (PubMed 23536163). Despite its potential, targeting LDH-5 presents challenges, including the need for high selectivity to avoid interfering with the enzyme's normal function in skeletal muscle and the liver, where it is also highly expressed (StatPearls NBK470179).

Other names

Lactate dehydrogenase ALDHALDH-ALDH-MMuscle-type lactate dehydrogenaseA4 isoenzyme

Inhibition of the conversion of pyruvate to lactate, reducing NAD+ regeneration, leading to glycolytic inhibition and metabolic stress in cancer cells.