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Glutamate dehydrogenase (GLDH)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Mitochondrial Liver-Enzyme Marker – Highly Specific for Hepatocellular Injury & Mitochondrial Damage)

Synonyms

  • GLDH
  • GLuDH
  • Glutamate dehydrogenase
  • α-ketoglutarate dehydrogenase (older term)
  • Mitochondrial liver enzyme
  • Oxidative deamination enzyme

Units of Measurement

GLDH activity may be reported in:

  • nkat/L
  • µkat/L
  • nmol/(s·L)
  • µmol/(s·L)
  • U/L
  • IU/L
  • µmol/(min·L)
  • µmol/(h·L)
  • µmol/(h·mL)

Unit Conversions (IFCC Enzyme Standards)

1 U/L = 1 IU/L
1 U/L = 16.67 nkat/L
1 nkat/L = 0.06 U/L
1 µmol/(min·L) = 60 U/L
1 µmol/(h·L) = 1 U/L
1 µmol/(h·mL) = 1000 U/L

(All conversions follow SI enzyme-activity recommendations.)

Description

Glutamate dehydrogenase (GLDH) is a mitochondrial enzyme located primarily in:

  • Liver (hepatocytes) → highest concentration
  • Kidney
  • Brain
  • Pancreas

Its presence in the blood is a highly specific marker of hepatocellular mitochondrial injury.

Because GLDH resides inside mitochondria, it is released only when severe liver cell injury occurs, making it a valuable marker in:

  • Acute liver failure
  • Drug-induced liver injury
  • Hypoxic hepatitis
  • Alcoholic hepatitis
  • NAFLD/NASH with necrosis

Physiological Role

GLDH catalyzes:

  • Oxidative deamination of glutamate → α-ketoglutarate + NH₄⁺
  • Key enzyme in amino acid metabolism
  • Links nitrogen and carbohydrate metabolism

It is highly abundant in zone 3 (centrilobular) hepatocytes, where most toxic injury occurs.

Clinical Significance

↑ GLDH (Elevated Levels)

Indicates mitochondrial hepatocellular injury.
More specific than ALT/AST.

1. Acute Liver Failure

Markedly elevated GLDH occurs in:

  • Hypoxic hepatitis (shock liver)
  • Severe ischemia
  • Viral hepatitis A, B, E
  • Drug-induced liver injury (acetaminophen, anti-TB drugs)

2. Alcoholic Hepatitis

Due to mitochondrial toxicity of ethanol.

3. NAFLD / NASH

GLDH rises earlier than ALT in necroinflammation.

4. Wilson Disease

Hepatocellular necrosis → high GLDH.

5. Sepsis & Multi-organ Failure

Due to hypoxic/ischemic liver damage.

6. Toxin Exposure

  • Amanita mushroom poisoning
  • Carbon tetrachloride
  • Hepatotoxic chemicals

7. Post–Cardiac Arrest or Shock States

Severe hypoxia → hepatocyte death → GLDH rise.

Normal or Low GLDH

  • Seen in mild liver disease
  • Normal in isolated cholestasis (ALP/GGT rise instead)
  • Helps differentiate hepatocellular vs cholestatic injury

Reference Intervals

(Tietz 8E + Mayo + ARUP + IFCC)
Values vary by method.

Adults (Typical Range)

  • < 7 U/L
    (or < 116 nkat/L)

Children

Similar or slightly lower depending on age.

Marked Elevation

  • >50 U/L → severe hepatocellular injury
  • >100 U/L → acute liver failure likely

Diagnostic Uses

1. Assess Hepatocellular Necrosis

GLDH is specific for mitochondrial damage, unlike ALT/AST.

2. Differentiating Hepatic vs Non-Hepatic Injury

  • ALT/AST may rise in muscle disease
  • GLDH is liver-specific

3. Alcoholic & Toxic Hepatitis

  • Mitochondrial toxins → GLDH elevation
  • More reliable than AST/ALT ratio

4. Hypoxic Liver Injury

  • GLDH strongly increases in ischemic hepatitis

5. Drug-Induced Liver Injury Monitoring

Useful for hepatotoxic medications:

  • Anti-TB drugs
  • Acetaminophen
  • Chemotherapy agents

6. NAFLD/NASH Severity Assessment

  • Higher GLDH → more necroinflammation

Analytical Notes

  • Serum sample
  • Hemolysis insignificant (mitochondrial enzyme)
  • Highly stable enzyme
  • More specific than ALT/AST for hepatic injury
  • IFCC-compliant kinetic assays recommended

Clinical Pearls

  • GLDH rises only when mitochondria are damaged → a sign of deep hepatocyte injury.
  • ALT and AST may remain mild while GLDH shows severe damage.
  • Very high GLDH strongly suggests acute liver failure or toxin-induced injury.
  • Normal GLDH with high ALP/GGT → likely cholestatic disease.
  • GLDH is not influenced by muscle injury, unlike AST.

Interesting Fact

Because GLDH is located in zone 3 hepatocytes (most oxygen-sensitive area), it is one of the best markers of hypoxic hepatitis.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Liver Enzymes.
  2. AASLD/EASL Guidelines on Drug-Induced Liver Injury.
  3. Mayo Clinic Laboratories - GLDH.
  4. ARUP Consult - Liver Injury Markers.
  5. IFCC Enzyme Standardization.
  6. MedlinePlus / NIH - Liver Function Tests.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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