Lactate dehydrogenase (LDH) is an enzyme found in nearly all living cells that reversibly converts pyruvate to lactate while interconverting NADH and NAD⁺. It is central to anaerobic energy metabolism, and blood LDH activity is measured as a general marker of tissue damage.

LDH (lactic acid dehydrogenase, L-lactate:NAD+ oxidoreductase) sits at the junction of glycolysis and cellular respiration. It lets cells make energy without oxygen by regenerating NAD+, and it lets tissues such as the heart and liver reuse lactate as fuel. Because LDH leaks into the blood when cells are damaged, its activity is a widely used, non-specific diagnostic marker. This guide explains what LDH is, what it does, how it differs from lactate, what a high LDH can mean, and how LDH activity is measured.

LDH, short for lactate dehydrogenase, is an oxidoreductase enzyme (EC 1.1.1.27 for the L-form) that catalyzes the reversible conversion between pyruvate and lactate, using NADH and NAD+ as its coenzyme pair. It is present in nearly all living cells, mainly in the cytoplasm.

The reaction it catalyzes is: pyruvate + NADH + H+ ⇌ L-lactate + NAD+. The direction it favors depends on the tissue, the oxygen supply, and the balance between NADH and NAD+.

LDH Isoenzymes

Human LDH exists as five isoenzymes, formed by different combinations of the H and M subunits. Their tissue distribution is the reason an LDH isoenzyme pattern can hint at the organ that is injured.

Tissue distribution is approximate; individual tissues contain more than one isoenzyme.

A separate enzyme, D-lactate dehydrogenase (EC 1.1.1.28), acts on D-lactate instead of L-lactate. It is used in assays for D-lactate; see the last section.

The core function of LDH is to interconvert pyruvate and lactate while regenerating NAD+ or NADH. This keeps glycolysis running when oxygen is limited and lets tissues recycle lactate as a fuel.

•     Anaerobic energy production. When oxygen is scarce, as in hard-working muscle, hypoxic tissue, and red blood cells (which have no mitochondria), LDH reduces pyruvate to lactate and regenerates the NAD+ that glycolysis needs to continue.

•     Lactate recycling. Lactate released by muscle travels to the liver, where LDH converts it back to pyruvate for gluconeogenesis (the Cori cycle).

•     Lactate as fuel. H-subunit-rich isoenzymes such as LDH-1 favor oxidizing lactate to pyruvate, which supports aerobic tissues like the heart.

•     Cancer metabolism. Many tumors raise LDH expression and favor lactate production even when oxygen is available, which is why LDH is studied as both a biomarker and a drug target.[1]

LDH is the enzyme; lactate is the molecule it produces and consumes. They are not the same, and tests for each answer different questions: an LDH test measures enzyme activity as a marker of tissue damage, while a lactate test measures lactate concentration as a marker of oxygen delivery and metabolic stress.

The names cause the confusion: LDH makes lactate, so both can rise in hypoxia, but one is a catalyst and the other a metabolite, and they can move independently. Note too that standard lactate methods detect L-lactate. D-lactate, produced by some gut bacteria, requires a D-lactate-specific method.

A high blood LDH level signals that cells somewhere in the body have been damaged and have released the enzyme, but it does not show which tissue or which disease is responsible. Results must be interpreted together with symptoms, other tests, and sometimes the LDH isoenzyme pattern.

LDH as a Cardiac Enzyme

After a myocardial infarction, heart cells release LDH, mainly LDH-1, and blood activity typically begins to rise within about a day, peaks over the following days, and stays elevated for one to two weeks. LDH was once a standard cardiac marker. Today cardiac troponin has replaced it for diagnosing heart attack because troponin is far more specific, so LDH plays only a minor, supporting role.

LDH in Liver Disease

Injury to liver cells releases LDH, mainly LDH-5, so levels can rise in hepatitis, ischemic liver injury, and hepatic congestion. LDH is less specific for the liver than ALT and AST, which is why it is read alongside them rather than alone.

Other Conditions Associated with High LDH

•     Blood disorders: hemolytic and megaloblastic anemias raise LDH sharply, and LDH is used to follow some lymphomas and leukemias.

•     Muscle and lung injury: skeletal muscle damage, pulmonary embolism, and some pneumonias can raise LDH.

•     Cancer: LDH is used as a prognostic or monitoring marker in several cancers, including some lymphomas, melanoma, and germ cell tumors.[1]

•     Body fluids: LDH in pleural fluid helps distinguish exudates from transudates.

Interpretation Tips

•     Hemolysis in the blood sample falsely raises LDH, so a hemolyzed specimen should be recollected.

•     Reference ranges differ between laboratories and methods; always use the range printed on the lab report.

This article is educational and is not medical advice. LDH results should be interpreted by a qualified clinician.

LDH activity is usually measured by spectrophotometry: the sample is mixed with substrate and NAD+ (or NADH), and the rate of NADH formation or consumption is tracked as the change in absorbance at 340 nm.

•     Pyruvate to lactate direction: LDH consumes NADH, so absorbance at 340 nm falls as the reaction proceeds.

•     Lactate to pyruvate direction: LDH produces NADH, so absorbance at 340 nm rises.

•     Dye-coupled colorimetric methods: NADH is used to reduce a tetrazolium dye to a colored formazan. This format is common in research assays that measure LDH released from damaged cells as an index of cytotoxicity.

Clinical analyzers typically use a kinetic (rate) measurement, which is less sensitive to sample background than a single endpoint reading. A typical reagent set contains buffer, substrate (lactate or pyruvate), and NAD+ or NADH.

Hzymes Reagents for Lactate Dehydrogenase Applications

Hzymes supplies lactate dehydrogenase for research and diagnostic assays. The current product, CAS 9028-36-8, is the D-lactate-specific form, which oxidizes D-lactate to pyruvate. It is used to measure D-lactate and to study D-lactic acidosis, a condition that standard L-lactate methods cannot detect.

View Hzymes biochemical diagnostic enzymes → 

1.      Review of LDH isoforms, biochemical properties, and clinical significance. Endocr Metab Immune Disord Drug Targets. 2020;20(6). PubMed 31886754.