What is the difference between lactic acid and lactic dehydrogenase (LDH)?

Difference Between Lactic Acid and Lactate Dehydrogenase (LDH)

Lactic acid and lactate dehydrogenase (LDH) are distinct biological molecules with different functions - lactic acid is a metabolic byproduct while LDH is the enzyme that catalyzes its conversion.

Lactic Acid

• Lactic acid is an organic acid produced during anaerobic glycolysis when oxygen supply is inadequate 1
• Depending on pH, it exists either as protonated acidic form (lactic acid) at low pH or as sodium salt (sodium lactate) at basic pH 1
• Functions as:
  • An energy source
  • A signaling molecule that can provide a "danger" signal in inflammatory conditions
  • A pH regulator 1
• Elevated blood lactate levels can serve as a chemical marker of disease severity in inflammatory conditions 1
• At physiological pH, lactic acid exists predominantly in its ionized form as lactate 1

Lactate Dehydrogenase (LDH)

• LDH is an enzyme that catalyzes the interconversion between pyruvate and lactate, using NAD+ as a coenzyme 2
• It is the terminating enzyme in the metabolic pathway of anaerobic glycolysis 1
• Exists as a tetrameric form composed of combinations of M(A) and H(B) subunits, forming different isoenzymes with tissue-specific distributions 3
• LDH is measured clinically using the JSCC recommendation method (lactate to pyruvate direction) 3
• Serum LDH is widely used as a marker enzyme that can predict mortality in many conditions including ARDS, severe COVID-19, and cancer 1

Key Differences

• Function: Lactic acid is a metabolite (substrate/product) while LDH is the enzyme that catalyzes its conversion 2
• Clinical significance:
  • LDH is measured as an enzyme activity in blood and used in Light's criteria to distinguish between transudative and exudative pleural effusions 4
  • Elevated LDH levels are associated with high tumor burden in conditions like plasma cell leukemia 4 and high-grade myeloma 5
  • LDH is included in Light's criteria where pleural fluid LDH >0.67 of the upper limit of normal serum value helps identify exudates 4
• Structure:
  • Lactic acid is a small organic molecule (C₃H₆O₃)
  • LDH is a large tetrameric protein composed of different combinations of subunits 3

Clinical Applications

• LDH in pleural effusion diagnosis:

  • Used in Light's criteria to differentiate exudates from transudates with 98% sensitivity and 72% specificity 4
  • Pleural fluid is considered an exudate if pleural fluid LDH divided by serum LDH is >0.6 or pleural fluid LDH >2/3 the upper limit of normal serum LDH 4

• LDH as a prognostic marker:

  • Elevated LDH is associated with poor prognosis in plasma cell leukemia 4
  • High serum LDH levels identify high-grade lymphoma-like myeloma with features of extraosseous disease and an unusually aggressive course 5
  • LDH is included in prognostic factors for staging Hodgkin's disease 4

Important Variants

• A distinct enzyme called lactate dehydrogenase D (LDHD) specifically catalyzes the oxidation of D-lactate to pyruvate and is associated with D-lactic acidosis when deficient 6
• LDHD is an Mn²⁺-dependent general dehydrogenase with activity for D-lactate and other D-2-hydroxyacids containing hydrophobic moieties 6

Laboratory Considerations

• LDH is commonly measured in clinical laboratories as an indicator of tissue damage 4
• LDH release assays are used to detect cell death by measuring the enzymatic activity of LDH released into culture supernatants or body fluids following plasma membrane breakdown 4
• The test measures enzymatic activity which can be affected by several variables including pH and components in the culture medium 4