LDH
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Lactate Dehydrogenase (LDH)
Biochemistry & Enzyme Properties
LDH (EC 1.1.1.27; L-lactate: NAD+ oxidoreductase) is a cytosolic hydrogen-transfer enzyme that catalyzes the reversible oxidation of L-lactate to pyruvate, using NAD+ as the hydrogen acceptor:
L-Lactate + NAD+ ⇌ Pyruvate + NADH + H+
- The reaction equilibrium strongly favors pyruvate → lactate (the "reverse reaction")
- Forward reaction (L→P) optimum pH: 8.8-9.8
- Reverse reaction (P→L) optimum pH: 7.4-7.8
- Molecular weight: 134 kDa
- Composed of 4 peptide chains of two types: M (muscle) and H (heart) subunits
- M subunit gene: chromosome 11
- H subunit gene: chromosome 12
- Inhibited by: thiol-reactive reagents (mercuric ions, p-chloromercuribenzoate), borate, oxalate, EDTA, and excess substrate (pyruvate > lactate)
Isoenzymes
LDH is separated into 5 major isoenzymes by electrophoresis (in order of decreasing anodal mobility in alkaline medium):
| Isoenzyme | Subunit Composition | Primary Tissue | Clinical Notes |
|---|---|---|---|
| LDH-1 | H4 (HHHH) | Heart, RBCs, Kidney | Elevated in AMI, hemolysis, renal infarction |
| LDH-2 | H3M | Heart, RBCs, Kidney | Normally highest in serum (LDH-2 > LDH-1) |
| LDH-3 | H2M2 | Lung, spleen, lymphocytes, pancreas | |
| LDH-4 | HM3 | Liver, skeletal muscle | Elevated in hepatic/muscle injury |
| LDH-5 | M4 (MMMM) | Liver, skeletal muscle | Elevated in hepatic/muscle injury |
Normal serum ratio: LDH-2 > LDH-1 > LDH-3 > LDH-4 > LDH-5
Additional isoenzymes:
- LDH-X (LDHc): Tetrameric X/C subunit; found in postpubertal testes; elevated in seminoma (LDH-1 is the most active isoenzyme in seminoma)
- LDH-6: Identified in serum of severely ill patients, migrates cathodal to LDH-5
Reference Range
- Upper limit of normal for total serum LDH: ~150 IU/L
- Levels >500 IU/L combined with elevated ALP (>250 IU/L) - without dramatic AST/ALT elevation - suggest space-occupying hepatic lesions (metastatic carcinoma, HCC, hemangioma)
Clinical Significance
LDH is a nonspecific marker of cellular injury/death, present in virtually all tissues.
Causes of Elevated Total LDH:
| Category | Conditions |
|---|---|
| Hematologic | Hemolysis, megaloblastic (pernicious) anemia, leukemia, lymphoma |
| Cardiac | Acute myocardial infarction |
| Hepatic | Hepatitis, space-occupying lesions, metastatic disease |
| Renal | Renal infarction |
| Muscle | Skeletal muscle injury, myopathy |
| Pulmonary | Pulmonary disease |
| Neoplastic | Germ cell tumors (especially seminoma), carcinomas |
| Other | Severe illness |
Isoenzyme-Specific Patterns:
- "Flipped LDH ratio" (LDH-1 > LDH-2): Classic for acute myocardial infarction, hemolysis, or renal infarction
- In AMI: LDH begins rising ~10 hours after onset, peaks at 24-48 hours, remains elevated up to 14 days
- Elevated LDH-4 & LDH-5: Liver damage or skeletal muscle injury
- Elevated LDH-1 (LDH-X): Seminoma of the testis (LDH-1/LDHc is highest in seminoma sera)
- Elevated LDH-3: Lymphoma, lung disease, pancreatic disease
Key Associations in Specific Conditions
- Malaria (severe): LDH used as a diagnostic/monitoring biomarker; P. falciparum produces its own LDH (pLDH) used in rapid diagnostic tests
- Pleural effusions: Pleural fluid LDH is part of Light's criteria for distinguishing exudates from transudates (exudate: pleural LDH > 2/3 upper limit of normal serum LDH)
- Obstetrics: LDH elevation in maternal serum is used in evaluation of anemia in pregnancy
- Psychiatry: Elevated LDH may be seen with liver, skeletal muscle, heart, and kidney disease - and in pernicious anemia
Sources: Tietz Textbook of Laboratory Medicine, 7th Ed. | Henry's Clinical Diagnosis and Management by Laboratory Methods | Quick Compendium of Clinical Pathology, 5th Ed. | Harrison's Principles of Internal Medicine, 22nd Ed. (2025)
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