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[Biochemistry](https://durgical.com/en/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](https://www.rcsb.org/structure/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](https://durgical.com/en/conditions/1-antitrypsin-deficiency/)
- [Chronic obstructive pulmonary disease (COPD)](https://durgical.com/en/conditions/chronic-obstructive-pulmonary-disease/)
- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)
- [Hepatocellular carcinoma](https://durgical.com/en/conditions/hepatocellular-carcinoma/)

## Related

- [Elastin](https://durgical.com/en/biochemistry/enzymes/elastin/)
- [Plasma proteins and electrophoresis](https://durgical.com/en/biochemistry/topics/plasma-proteins-and-electrophoresis/)
- [Protein structure and folding](https://durgical.com/en/biochemistry/topics/protein-structure-and-folding/)
- [Types of enzyme inhibition](https://durgical.com/en/biochemistry/topics/types-of-enzyme-inhibition/)

## 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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [SERPINA1: Alpha-1-antitrypsin (human)](https://www.uniprot.org/uniprotkb/P01009/entry) (UniProt, 2026); [SERPINA1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/serpina1/) (MedlinePlus, US National Library of Medicine, 2026); [1QLP: 2.0 ANGSTROM STRUCTURE OF INTACT ALPHA-1-ANTITRYPSIN: A CANONICAL TEMPLATE FOR ACTIVE SERPINS](https://www.rcsb.org/structure/1QLP) (RCSB Protein Data Bank, 2026); [PDB-101: Molecule of the Month: Serpins](https://pdb101.rcsb.org/motm/53) (RCSB Protein Data Bank (PDB-101), 2026); [Alpha-1 antitrypsin blood test: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003715.htm) (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.

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Source: https://durgical.com/en/biochemistry/enzymes/1-antitrypsin/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/1-antitrypsin/