Secretion of hepatic and intestinal alkaline phosphatases: Similarities and differences

Abstract

The presence of plasma membrane-bound proteins in the serum of mammals has been noted for many years. Examples of such proteins include alkaline phosphatase (liver, bone, intestinal, and placental) [l], 5’-nucleotidase [2], and gamma-glutamyl transferase [3]. The mechanism of attachment of these proteins to the membrane is now fairly clear. Some proteins, e.g. gamma-glutamyl transferase, are attached to the plasma membrane by a hydrophobic transmembrane sequence [4]. Other proteins, including the alkaline phosphatases (AP), are bound by the fatty acid portion of a phosphatidylinositol-glycan anchor [5]. In spite of this information the mechanism for release of these enzymes from the membrane is not known. Moreover, because secretion is stimulated by factors unique to each organ, the mechanism(s) may differ from organ to organ, e.g. liver and intestine. A variety of suggestions have been offered to explain enzyme release, including detergent action, proteolysis, membrane fragmentation [6], or lipolysis [5]. Detergent action has been suggested most often for hepatocyte membrane proteins, because high concentrations of bile salts are present [7]. Normally the sinusoidal and canalicular alkaline phosphatases are secreted into the blood and bile respectively [S]. The enzyme in bile appears to be particulate [9], whereas that in the blood is largely soluble. The original interpretation of these data were that the sinusoidal enzyme was released by detergent action. However, recent work has shown that solublization with butanol was due not to detergent-like action, but to the activation of tissue phospholipase C that released fatty acids from the AP [lo]. Proteins attached to the membrane by a transmembrane segment could be released by the action of proteases in the membrane or in the surrounding fluid. Cell