Further Evidence on the Subcellular Sites of Kininase II (Angiotensin Converting Enzyme)

Abstract

There is an abundant indirect evidence indicating that circulating bradykinin and angiotensin I are metabolized by enzymes situated along the luminal surface of pulmonary endothelial cells (for reviews, see Ryan, et al., 1970a, 1972a & b; Smith & Ryan, 1973; Ryan & Ryan, 1975). The metabolism of bradykinin results in loss of biological activity, but the activity of angiotensin I is enhanced, in part by conversion to its lower homolog, angiotensin II. Recently, Dorer, et al. (1972, 1974a) have succeeded in isolating an enzyme (angiotensin converting enzyme or kininase II) from pig lung which has the capacity of metabolizing angiotensin I and bradykinin to produce metabolites like those produced by intact lungs: The enzyme converts angiotensin I to angiotensin II by releasing the C-terminal dipeptide, His-Leu, and inactivates bradykinin by releasing the C-terminal dipeptide, Phe-Arg (cf Ryan, et al., 1969, 1970a & b, 1971). Furthermore, the enzyme shows the same selectivity of metabolism as was observed with intact lungs: none of the higher homologs of bradykinin is inactivated as fast as is bradykinin itself (Ryan,et al., 1970a; Roblero,et al., 1973; Dorer,et al., 1974b). Inactivation of the homologs appears to vary inversely with size and charge.