Biochemistry · Protein
α1-antitrypsin !
α1-antitrypsin, made in the liver, restrains neutrophil elastase and protects the lung; when it misfolds, it damages the liver too.
Updated 2026-11-01
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Key facts
- A serpin (serine protease inhibitor) of 394 amino acids, a glycoprotein made mostly by hepatocytes; SERPINA1 gene on chromosome 14.
- Its main target is neutrophil elastase; it is the main component of the α1 band on electrophoresis.
- It works as a trap: the protease cuts the reactive loop (Met358), the loop inserts into a β-sheet and drags the protease along, leaving it distorted and inactive.
- The Z allele (Glu342Lys) makes the protein polymerise in the hepatocyte ER: little protein in blood (emphysema) and deposits in the liver (cirrhosis).
- Cigarette smoke oxidises Met358 and inactivates it.
- Also called
- Alpha-1 antitrypsin, α1-proteinase inhibitor (α1-PI), Serpin A1
- Genes
- SERPINA1
- Structure (PDB)
- 1QLP
Structure
- Structure 1QLP is intact, active human α1-antitrypsin (2.0 Å): a large central β-sheet (A) and the reactive-centre loop exposed on top, ready to trap the protease.
- There is no small ligand: the “target” is another protein; the model highlights the serpin fold.
Regulation
- An acute-phase reactant: its synthesis rises several-fold in inflammation (IL-6).
- Codominant inheritance: each allele makes its own protein (M normal, S slightly low, Z very low, null alleles none).
Inhibitors and toxins
- Oxidation of Met358 by cigarette smoke and neutrophil oxidants
- Polymerisation of Z and other variants (loss of function and retention)
Clinical notes
- α1-antitrypsin deficiency (PiZZ): basal panacinar emphysema before 45, especially in smokers, and liver disease from infancy.
- Liver biopsy shows PAS-positive, diastase-resistant globules (retained Z protein).
- It should be sought in any young patient with COPD, basal emphysema or a family history, and in liver disease without a clear cause.
Related conditions
- α1-antitrypsin deficiency
- Chronic obstructive pulmonary disease (COPD)
- Cirrhosis
- Hepatocellular carcinoma
Related
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme does α1-antitrypsin mainly inhibit?
Neutrophil elastase, which, if left free, destroys the elastin of alveolar walls.
Why does the Z variant damage both liver and lung?
It polymerises in the hepatocyte (liver damage from retention) and barely reaches the blood (the lung is left unprotected).
Why does smoking make α1-antitrypsin deficiency much worse?
Smoke oxidises Met358 in the reactive loop, inactivating what little protein there is, and draws in elastase-laden neutrophils.
In which electrophoresis band is α1-antitrypsin seen?
The α1 band, of which it is the main component; in deficiency that band is very low.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: SERPINA1: Alpha-1-antitrypsin (human) (UniProt, 2026); SERPINA1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 1QLP: 2.0 ANGSTROM STRUCTURE OF INTACT ALPHA-1-ANTITRYPSIN: A CANONICAL TEMPLATE FOR ACTIVE SERPINS (RCSB Protein Data Bank, 2026); PDB-101: Molecule of the Month: Serpins (RCSB Protein Data Bank (PDB-101), 2026); Alpha-1 antitrypsin blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.