METABOLISM OF ENTEROSTATIN IN RAT INTESTINE, BRAIN MEMBRANES, AND SERUM - DIFFERENTIAL INVOLVEMENT OF PROLINE-SPECIFIC PEPTIDASES

The degradation of enterostatin (VPDPR), a potent inhibitor of food in take, by intestinal brush-border membranes, brain membranes, and rat s erum has been investigated in the presence of specific inhibitors. Hyd rolysis by intestinal membranes was found to be 10 and 100 times faste r than in serum and brain membranes, respectively. Enterostatin hydrol ysis by intestinal and brain membranes involves the removal of C-termi nal arginine by carboxypeptidase P, leading to the production of des-A rg-enterostatin, and the splitting of the pro(2)-Asp(3) bond by dipept idyl aminopeptidase IV (DPP IV). A small amount of the potent anorecti c peptide Pro(2)-Asp(3)-Pro(4) was released during hydrolysis of des-A rg-enterostatin by brain membranes and rat serum. In rat serum, entero statin degradation was mainly due to DPP IV.