Lactate Dehydrogenase Overview

Lactate Dehydrogenase (LDH)

• LDH is an important enzyme in anaerobic metabolism
• It belongs to the oxidoreductase class, EC 1.1.1.27
• Catalyzes the reversible conversion of lactate to pyruvate, reducing NAD+ to NADH
• Found in all tissues, a key checkpoint in gluconeogenesis and DNA metabolism
• Increased LDH may indicate liver disease, anemia, heart attack, bone fractures, muscle trauma, cancers, infections (encephalitis, meningitis, encephalitis, HIV)

LDH as a Diagnostic Marker

• LDH can be a non-specific marker for tissue turnover
• Elevated levels or specific isozyme increases can suggest cancer but are not diagnostic of type
• Needs additional tests (e.g., CK for muscle; ALT for liver; troponin for heart)
• Hemolysis of blood sample can increase LDH levels artificially; red blood cells contain LDH
• Cellular necrosis also increases LDH serum concentration
• LDH is a cytoplasmic enzyme found in all tissues but high concentrations in muscle, liver, and kidney; red blood cells also contain moderate amounts

LDH Isozymes

• LDH exhibits five isomeric forms (LDH-1 to LDH-5) based on the number of muscle (M) and heart (H) subunits
• Each isozyme has varying expression in different tissues.
• LDH-1 is primarily in the heart, LDH-2 in reticuloendothelial systems (RBCs), LDH-3 in lungs, LDH-4 in kidneys, and LDH-5 in liver and skeletal muscle
• The subunit composition influences substrate affinity, inhibition, isoelectric point, and electrophoretic mobility

LDH at a Molecular Level

• Four genes (LDHA, LDHB, LDHC, LDHD) encode for LDH
• LDHA, LDHB, and LDHC produce L-forms (major form in vertebrates)
• LDHD produces D-isomer of LDH
• LDH-1 to LDH-5 are translational products of LDHA and LDHB genes
• Four subunits (combinations of A and B) form the five different LDH forms

LDH Function in Different Conditions

• In anaerobic conditions (e.g., exercise, hypoxic conditions) cells utilize LDH to produce lactate from pyruvate
• LDH catalyzes the reversible conversion of pyruvate to lactate using NADH
• LDH is necessary for lactate conversion back to pyruvate in the liver (Cori cycle)

LDH Function in Cancer

• Cancer cells often have increased glycolysis (Warburg effect) and LDH activity to compensate for low oxygen conditions
• LDH-5, especially, is associated with certain cancers and may be a marker for radio-sensitization

Clinical Significance of LDH

• LDH assays measure the amount of LDH in serum, which leaks from damaged tissues
• Measuring the change in optical density at 340 nm due to NADH production is how reaction rate is estimated
• LDH levels are typically 140-280 U/L, but values vary with conditions and age
• Elevated or specific isozyme elevations can suggest various diseases (e.g., liver disease, kidney disease, muscle damage, heart attack, etc.), as well as cancer, inflammations, and other diseases
• LDH is used for cancer staging, evaluating metastatic cancer, and assessing muscle response to training