α1-Antitrypsin: Structure, Function, Physiology

The carboxyl-terminal fragment of α1-Antitrypsin (α1-AT) and the other serpins bears important structural and functional chracteristics. Structural variants of α1-AT in humans are classified according to the protease inhibitor phenotype system as defined by agarose electrophoresis or isoelectric focusing of plasma. α1-AT acts competitively by allowing its target enzyme to attack a substrate-like sequence in the carboxyl-terminal region of the inhibitor molecule. The concentration of α1-AT in lavage fluid from the lower respiratory tract is approximately equivalent to that in serum. Plasma concentrations of α1-AT also increase during oral contraceptive therapy and pregnancy. Comparison of α1-AT to other members of the serpin family has generated several important concepts of the structure and function of α1-AT. α1-AT is the archetype of a family of proteins, serpins, which form covalently stabilized complexes with their cognate serine proteases. α1-AT also inhibits neutrophil cathepsin G and may inhibit several serine proteases derived from mast cells and cytolytic T-lymphocytes.