The interaction of hydrophobic bile acids with the α1‐proteinase inhibitor

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Abstract
An in vitro complex formation between cholesterol and human α1‐proteinase inhibitor (α1‐antitrypsin, α1‐Pi) has been described. Hydrophobie bile acids were studied for a similar interaction using lithocholic acid (LC) as a prototype of a hydrophobic acid. At a molar ratio of 5:1, LC induced conformational changes of α1‐Pi reflected in an abnormal gel‐electrophoretic appearance, loss of anodal immunoreactivity on crossed immunoelectrophoresis, exposition of new antigenic determinant(s) on immunodiffusion, and loss of antiproteinase activity. After 6 h incubation, LC and α1‐Pi form a complex of approximately 200 kDa molecular mass seen following gel‐filtration. After prolonged (24 h) interaction a series of large α1‐Pi polymers were seen on SDS‐PAGE under reducing conditions followed by Western blotting. Glycolitho‐, sulfolitho‐, deoxycholic and 3‐β‐hydroxy‐5‐cholenoic acids induced similar but less pronounced changes of α1‐Pi, whereas transferrin remained unaffected. Hydrophilic acids lacked effect on α1‐Pi. The results are compatible with a specific, irreversible interaction of α1‐Pi with hydrophobic bile acids affecting its physical and proteinase inhibitory properties. The cholestatic potency of the hydrophobic acids studied and their ability to induce α1‐Pi polymerization may be important in cholestatic conditions.