A neutral protease from rat intestinal muscle. A possible role in the degradation of native enzymes

Abstract

A membrane-limited protease has been solubilised and partially purified from the intestinal smooth muscle of rats fed on protein free diets. This neutral protease has a mol. wt. of around 33,000 and from its susceptibility to several known modifiers of proteolytic enzymes, it appears to be trypsin-like. It is stable over a relatively narrow pH range and it appears to have a markedly enhanced ability over trypsin for inactivating substrate enzymes in their native conformations through limited proteolysis. The rate of inactivation of substrate enzymes can be modulated by cofactors, allosteric ligands, or by changes in ionic strength. In addition, a specific protein inhibitor of the protease has been measured and levels of this are high in animals fed on normal diets. On administration of protein free diets, the inhibitory activity is depleted. Contamination of the muscle tissue by lumenal, mucosal or blood proteases and inhibitors has been excluded. A role for the neutral protease in initiating the turnover of intracellular enzymes is postulated.