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Alcohol Dehydrogenase (ADH)
(Ethanol Dehydrogenase – Enzyme Marker for Alcohol Metabolism & Toxicology)
Synonyms
- ADH
- Alcohol dehydrogenase
- Ethanol dehydrogenase
- Aldehyde-forming oxidoreductase
- Ethanol → Acetaldehyde enzyme
Units of Measurement
nkat/L, µkat/L, nmol/(s•L), µmol/(s•L), U/L, IU/L, µmol/(min•L), µmol/(h•L), µmol/(h•mL)
Description
Alcohol Dehydrogenase (ADH) is a zinc-dependent enzyme found mainly in:
- Liver (primary site)
- Stomach
- Kidney
- Pancreas
- Lung
ADH catalyzes the oxidation of ethanol to acetaldehyde:
It plays a central role in alcohol metabolism, particularly in the early stages after alcohol intake.
Measurement of ADH levels or activity in serum is useful in:
- Alcohol intoxication
- Acute ethanol poisoning
- Evaluating liver injury
- Severe alcoholic hepatitis
- Differentiating causes of elevated ethanol levels
Physiological Role
1. Ethanol Metabolism
ADH is the first major enzyme in alcohol metabolism, followed by:
- Aldehyde dehydrogenase (ALDH)
- Microsomal ethanol oxidizing system (MEOS – CYP2E1)
2. Toxicology
Serum ADH increases in acute alcohol ingestion, liver damage, and certain metabolic conditions.
3. Liver Function
High ADH activity correlates with hepatocellular injury, making it a supplemental marker alongside ALT, AST, and GGT.
Clinical Significance
Increased ADH
Seen in:
1. Alcohol Intoxication
- Recent heavy drinking
- Acute ethanol toxicity
- High blood alcohol concentrations
2. Liver Diseases
- Alcoholic hepatitis
- Cirrhosis
- Acute liver injury (viral, drug-induced)
- Fatty liver disease
3. Other Conditions
- Pancreatitis
- Severe burns
- Tissue necrosis
4. Genetic Variants
People with ADH1B*2 or ADH1C*1 variants metabolize alcohol faster → higher ADH levels.
Decreased ADH
Not typically clinically significant but may occur with:
- Advanced cirrhosis (hepatocyte loss)
- Severe malnutrition
- Late-stage alcoholic liver disease
Reference Intervals
(Tietz 8E + IFCC enzymology + Mayo Clinic toxicology)
ADH reference intervals vary widely due to different assay methods.
Typical serum range:
Adults
- < 25 U/L (method dependent)
- SI equivalent: < 417 nkat/L
Many labs do not report ADH routinely; ethanol levels are preferred for diagnosis of intoxication.
Toxicology Notes
- ADH rises rapidly after alcohol consumption (1–3 hours).
- Peak activity correlates with peak ethanol conversion.
Diagnostic Applications
1. Alcohol Intoxication
ADH can supplement ethanol testing when ethanol evaporates or is degraded during transport.
2. Alcoholic Hepatitis
High ADH activity may help differentiate alcoholic hepatitis from other liver diseases.
3. Biomarker of Alcohol Use
ADH isoenzyme patterns differ in chronic vs binge drinkers.
4. Forensic & Toxicology
Useful when ethanol testing is unavailable or sample integrity is questionable.
Isoenzymes of ADH
There are multiple isoenzymes (Class I–V):
- Class I (ADH1): Main hepatic form; predominant in alcohol metabolism
- Class II: High Km; active at high ethanol concentrations
- Class III: Formaldehyde detoxification
- Class IV: Present in upper GI tract
- Class V: Less understood; low activity
Genetic polymorphisms influence alcohol tolerance and alcohol-related disease risk.
Unit Meanings
| Unit | Meaning |
| nkat/L | nanokatal per liter (SI) |
| µkat/L | microkatal per liter |
| nmol/(s•L) | nanomole per second per liter |
| µmol/(s•L) | micromole per second per liter |
| U/L or IU/L | enzyme units per liter |
| µmol/(min•L) | micromole per minute per liter |
| µmol/(h•L) | micromole per hour per liter |
| µmol/(h•mL) | micromole per hour per milliliter |
Conversions (IFCC Enzyme Standards)
- 1 U/L = 16.67 nkat/L
- 1 nkat/L = 0.06 U/L
- 1 µkat/L = 60 U/L
Time conversions:
- µmol/(min•L) × 60 = µmol/(h•L)
- µmol/(h•L) ÷ 1000 = µmol/(h•mL)
Analytical Notes
- ADH is measured using spectrophotometric or enzymatic kinetic assays.
- Not a primary liver test — used selectively in toxicology.
- Ethanol measurement directly is more reliable, but ADH may complement it.
- Hemolysis and lipemia can interfere with ADH measurement.
Clinical Pearlsh
- ADH rises shortly after drinking → useful in early intoxication.
- ADH activity decreases with advanced cirrhosis (loss of hepatocytes).
- Genetic variants influence alcohol metabolism speed.
- High ADH + high GGT suggests chronic alcohol use or alcoholic hepatitis.
- ADH measurement may help identify recent drinking even when ethanol has been metabolized.
Interesting Fact
Alcohol dehydrogenase evolved over 500 million years ago and is found in organisms from plants to humans. Early primates developed highly active ADH isoenzymes to metabolize fermented fruits, influencing human alcohol tolerance today.
References
- Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition - Enzymes & Toxicology Section.
- IFCC Guidelines - Enzyme activity standardization.
- Mayo Clinic Laboratories - Alcohol Dehydrogenase Test.
- ARUP Consult - Alcohol Toxicology Interpretation.
- NIH / NIAAA - Alcohol Metabolism Pathways.
- Li TK et al. “Genetic polymorphisms of ADH and ALDH.” Alcohol Res Health.
- Clinical Toxicology Texts - Ethanol poisoning and ADH kinetics.