Isorenin, pseudorenin, cathepsin D and renin. A comparative enzymatic study of angiotensin-forming enzymes.
1. Renin was purified 30 000-fold from rat kidneys by chromatography on DEAE-cellulose and SP-Sephadex, and by affinity chromatography on pepstatinyl-Sepharose. 2. The enzymatic properties of isorenin from rat brain, pseudorenin from hog spleen, cathepsin D from bovine spleen, and renin from rat kidneys were compared: Isorenin, pseudorenin and cathepsin D generate angiotensin from tetradecapeptide renin substrate with pH optima around 4.9, renin at 6.0. With sheep angiotensinogen as substrate, isorenin,  pseudorenin and cathepsin D have similar pH profiles (pH optima at 3.9 and 5.5), in contrast to renin (pH optimum at 6.8). 3. The angiotensin-formation from tetradecapeptide by isorenin, pseudorenin and cathepsin D was inhibited by albumin, alpha-and beta-globulins. These 3 enzymes have acid protease activity at pH 3.2 with hemoglobin as the substrate. Renin is not inhibited by proteins and has no acid protease activity. 4. Renin generates angiotensin I from various angiotensinogens at least 100 000 times faster than isorenin, pseudorenin or cathepsin D, and 3000 000 times faster than isorenin when compared at pH 7.2 with rat angiotensinogen as substrate. 5. The 3 'non-renin' enzymes exhibit a high sensitivity to inhibition by pepstatin (Ki less than 5.10(-10) M), in contrast to renin (Ki approximately 6-10(-7) M), at pH 5.5. 6. It is concluded from the data that isorenin from rat brain and pseudorenin from hog spleen are closely related to, or identical with cathepsin D.
D000418:Albumins / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism; D000809:Angiotensins / Q000096:biosynthesis*; D000818:Animals; D002403:Cathepsins / Q000378:metabolism*; D002417:Cattle; D010450:Endopeptidases; D007700:Kinetics; D008297:Male; D010436:Pepstatins / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000378:metabolism*; D013552:Swine
D000418:Albumins; D000809:Angiotensins; D010436:Pepstatins; D000808:Angiotensinogen; D002403:Cathepsins; D010450:Endopeptidases; D012083:Renin; C015306:iso-renin; C003241:pseudorenin