LDHA Full Name
lactate dehydrogenase A
LDHA Introduction
LDHA is a member of the lactate dehydrogenase (LDH) isoenzyme family. LDH is a tetrameric protein composed of two main subunits—the A subunit (also called the M subunit, predominantly expressed in muscle) and the B subunit (also called the H subunit, predominantly expressed in heart)—assembled in various combinations. The LDHA gene encodes the A subunit; therefore, the isoenzyme composed of four A subunits (LDH-5 or M4) primarily carries out LDHA's function. This isoenzyme is mainly found in tissues such as skeletal muscle and liver that frequently experience hypoxia or engage in high-intensity anaerobic metabolism. Its core catalytic function lies in the final step of the glycolytic pathway: reversibly converting pyruvate to L-lactate while oxidizing one molecule of NADH to NAD⁺. LDHA is not merely the endpoint of glycolysis but also a critical node linking glycolysis with other cellular metabolic pathways and maintaining intracellular redox balance.
Figure 1. The canonical and moonlighting functions of LDHA. (Source: Lv L, et al. 2021)
First, by controlling the fate of pyruvate, LDHA directly influences the cell's choice of energy production mode. In cells with high glycolytic flux, such as vigorously contracting muscle cells or tumor cells, LDHA converts large amounts of pyruvate into lactate, thereby diverting pyruvate from entering the mitochondrial tricarboxylic acid (TCA) cycle. Although this pathway yields less ATP per glucose molecule (glycolysis produces 2 ATP, compared to ~36 ATP via aerobic oxidation), its reaction rate is extremely rapid, meeting urgent cellular energy demands. Second, LDHA is crucial for maintaining cellular redox homeostasis. The cytosolic NADH/NAD+ ratio is a key metabolic regulatory parameter that affects the rate and direction of hundreds of redox reactions. Through its catalytic reaction, LDHA directly regulates the cytosolic NADH/NAD+ ratio. When rapid consumption of NADH is required—for instance, under high glycolytic flux—LDHA activity increases. Conversely, when cells need more NADH for reductive biosynthesis, LDHA activity or the conversion of pyruvate to lactate may be suppressed. This dynamic regulation of redox state is vital for cells to adapt to varying metabolic needs and resist oxidative stress.
The expression and activity of LDHA are tightly regulated by various factors to adapt to changes in the intra- and extracellular environment. At the transcriptional level, one of the most important regulators is hypoxia-inducible factor 1 (HIF-1). Under hypoxic conditions, the HIF-1α subunit is stabilized and forms a heterodimer with HIF-1β, translocating into the nucleus and binding to hypoxia response elements (HREs) in the promoter regions of multiple glycolytic genes, including LDHA, thereby upregulating their transcription. This constitutes a core mechanism of cellular adaptation to hypoxia, ensuring that energy production can be sustained via enhanced glycolysis when oxygen supply is limited. Additionally, key oncogenes and tumor suppressor genes directly or indirectly regulate LDHA expression. For example, the oncogenic transcription factor c-Myc can directly bind to the LDHA gene promoter, activating its transcription—one important pathway through which c-Myc drives metabolic reprogramming in cancer cells. Conversely, the tumor suppressor p53 can inhibit LDHA expression. This regulatory network intimately links LDHA with core signaling pathways governing cell proliferation, apoptosis, and transformation.
Alternate Names for LDHA
LDHA
lactate dehydrogenase A
LDH1
LDHM
GSD11
PIG19
HEL-S-133P
L-lactate dehydrogenase A chain
LDH-A
LDH-M
