Lactate Dehydrogenase · What Is It, Function, Treatment, and More

Lactate dehydrogenase (LDH), also known as lactic acid dehydrogenase, is an oxidoreductase enzyme, a class of enzymes that can transfer electrons between molecules. During glycolysis, glucose is transformed into pyruvate, which is metabolized to produce adenosine triphosphate (ATP) through the citric acid cycle and oxidative phosphorylation. When oxygen is absent or limited, LDH catalyzes the conversion of pyruvate to lactate through a reversible reaction known as the anaerobic pathway.  

LDH is present in nearly all tissues in the body, with skeletal muscle cells responsible for around 40% of the total lactate production. Since LDH is present in most tissues, the measurement of LDH in the blood can signify tissue turnover and is a non-specific way of determining tissue injury within the body. 

When oxygen is not present (i.e., anaerobic conditions), the citric acid cycle cannot proceed, and cells generate energy through anaerobic glycolysis. In this pathway, LDH catalyzes the reduction of pyruvate to lactate, converting NADH to NAD+. The regeneration of NAD+ is necessary for energy production in the absence of oxygen. Once lactate is produced, it enters the bloodstream and is transported to the liver to be recycled in the Cori cycle (i.e., lactic acid cycle).  

In the liver, the reversible LDH enzyme converts lactate back into pyruvate, converting NAD+ to NADH in the process. Once pyruvate is created, it can be metabolized to regenerate glucose in the liver. Glucose is then transported to other tissues in the body, such as to muscles, where it can be broken down to produce energy. The net ATP produced during anaerobic metabolism is only 2 ATP per glucose molecule, compared to 36 ATP generated during aerobic metabolism. 

Lactate dehydrogenase can be measured from blood or fluids from the body. The test measures the amount of LDH that has leaked from damaged cells. A healthcare professional can draw blood inserting a small needle into a vein and analyzing the sample using the LDH blood test.  

LDH can also be measured from other body fluids including cerebrospinal fluid, pleural effusion fluid, and abdominal fluid. LDH is measured in units per liter, and for adults, a normal LDH range is typically 122 to 222 units per liter, depending on the laboratory and assay used. 

Most commonly, elevated LDH levels are caused by exercise or strenuous activity. During exercise, muscles may not receive enough oxygen to meet their energy demands, and muscle cells will often turn to anaerobic metabolism for energy. Elevated LDH can also indicate ongoing tissue damage from more serious underlying conditions. For instance, cancer cells require high levels of energy to sustain their constant replication and often switch from oxidative phosphorylation to anaerobic metabolism (Warburg effect).  

LDH can also be elevated in conditions affecting the respiratory system (e.g., pulmonary embolism), hematologic system (e.g., lymphoma, leukemia, anemia), and cardiac system (e.g., heart attack). Other causes of elevated LDH include trauma, gastrointestinal system disease (e.g., pancreatitis, liver disease), kidney disease, or infectious disease (e.g., malaria, encephalitis, meningitis, HIV). The levels of LDH change with the severity of disease, so healthcare providers may use it as a non-specific marker for prognosis or to determine if treatment is working. 

LDH can also be falsely elevated due to certain medications (e.g., narcotics, procainamide, aspirin) and alcohol.