SERPINA1

Alpha 1 Antitrypsin is classified as a protease inhibitor. It is also referred to as alpha1–proteinase inhibitor (A1PI) or alpha1-antiproteinase (A1AP) because it inhibits various proteases, not just trypsin . As a member of the serpin superfamily, it shares structural and functional characteristics with other serine protease inhibitors .

A1AT is a glycoprotein with a molecular weight of approximately 52 kDa. It is composed of 394 amino acids and contains three carbohydrate side chains . The protein’s primary function is to inhibit neutrophil elastase, an enzyme that can degrade elastin and other structural proteins in the lungs .

A1AT is predominantly produced in the liver, but it is also synthesized in other tissues, including the bone marrow, lymphoid tissue, and the Paneth cells of the gut . Once produced, it enters the systemic circulation and can be found in various body fluids, including blood, lymph, and alveolar fluid .

The primary function of A1AT is to protect tissues from enzymes released by inflammatory cells. Neutrophil elastase, in particular, can cause significant tissue damage if not regulated. A1AT binds to and inhibits this enzyme, preventing it from degrading elastin and other extracellular matrix components . This protective role is especially important in the lungs, where unchecked elastase activity can lead to conditions such as chronic obstructive pulmonary disease (COPD) and emphysema .

A1AT inhibits neutrophil elastase through a mechanism known as suicide inhibition. In this process, A1AT forms a stable complex with the enzyme, rendering it inactive . This interaction involves the cleavage of a specific peptide bond within A1AT, leading to a conformational change that traps the enzyme .

The expression of A1AT is regulated at both the transcriptional and post-transcriptional levels. Various factors, including cytokines and acute-phase reactants, can influence its production . During inflammation or infection, the levels of A1AT in the blood can increase significantly as part of the acute-phase response .

Alpha 1 Antitrypsin Deficiency (AATD) is a genetic disorder characterized by low levels of A1AT in the blood. This condition can lead to severe lung and liver diseases . Individuals with AATD are at increased risk of developing COPD, emphysema, and liver cirrhosis . The deficiency is caused by mutations in the SERPINA1 gene, which result in the production of misfolded A1AT that accumulates in the liver and fails to reach the bloodstream .

A1AT is used therapeutically to treat individuals with AATD. The pharmaceutical form of A1AT is purified from human donor blood and is administered to patients to increase the levels of functional A1AT in their blood . This treatment helps to protect the lungs from damage caused by neutrophil elastase and can slow the progression of lung disease .