Release of membrane-bound enzymes from cells and the generation of isoforms

Abstract

Enzymes bound to the surfaces of cells may be retained by a hydrophobic amino acid sequence (e.g. gamma-glutamyltransferase) or by a specific glycan phosphatidylinositol (GPI) anchor (e.g. alkaline phosphatase). In either case the attachment is by means of non-covalent hydrophobic interactions between the anchoring domain of the enzyme and lipid components of the cell membrane. Enzyme molecules released into the plasma or bile, complete with their hydrophobic domains, can undergo aggregation and complexation to give rise to high molecular weight isoforms of gamma-glutamyltransferase or alkaline phosphatase. However, the GPI domain of alkaline phosphatase can be degraded by an inositol-specific phospholipase in plasma, but not in bile, with production of the hydrophobic, non-aggregating isoform of alkaline phosphatase that predominates in plasma.