A DISTINCT PEPTIDYL DIPEPTIDASE THAT DEGRADES ENKEPHALIN - EXCEPTIONALLY HIGH-ACTIVITY IN RABBIT KIDNEY

Peptidyl dipeptidase activity distinct from the angiotensin converting enzyme (EC 3.4.15.1) was isolated from membrane fractions of rabbit kidney and lung. The enzyme cleaved Leu-enkephalin at the Gly-Phe bond, releasing Tyr-Gly-Gly and Phe-Leu, and also acted on bradykinin releasing the terminal dipeptide Phe-Arg. In contrast to the converting enzyme, this peptidyl dipeptidase did not act on angiotensin I, or on hippuryl His-Leu, nor was it inhibited by captopril (SQ 14225) or by SQ 20881 [teprotide]. Kinetic studies indicated a Km for the kidney enzyme of 80 .mu.M with Leu-enkephalin as a substrate. Evidently more than 1 enzyme is present in membrane preparations of lung and kidney inactivating enkephalin; these enzymes may be involved in the peripheral actions of opiate and related peptides.