antichymotrypsin

Antichymotrypsin, also known as alpha-1-antichymotrypsin (ACT), is a secreted serine protease inhibitor belonging to the serpin superfamily. In humans, it is encoded by the SERPINA3 gene. ACT is produced primarily by the liver but is also expressed by astrocytes and other tissues, and it functions as an acute-phase protein whose circulating levels rise during inflammation.

Mechanism of action: As a suicide substrate inhibitor, ACT binds to chymotrypsin-like serine proteases, notably chymotrypsin and neutrophil cathepsin G, forming a stable covalent complex that inactivates the protease. This helps regulate extracellular proteolysis and protect tissues during inflammatory responses.

Clinical significance: In Alzheimer's disease, alpha-1-antichymotrypsin has been found in association with amyloid plaques and is considered an amyloid-associated protein that can promote amyloid-beta aggregation. Serum ACT levels increase in many inflammatory conditions and may serve as an acute-phase biomarker. Deficiency of ACT is rare and not a common clinical syndrome, but genetic variation in SERPINA3 can influence expression levels in some contexts.

Genetics and structure: ACT is encoded by SERPINA3 on chromosome 14 and is a glycoprotein with several N-linked glycan chains. It is one of several serpins that regulate protease activity in the extracellular milieu.