Converting Enzyme in Vitro Measurement and Properties

Abstract

In 1954 Skeggs, Marsh, Kahn and Shumway reported that angiotensin, the pressor product of renin’s incubation with its substrate, was actually a mixture of two forms, Ang. I and Ang. II, separable by counter-current distribution. Ang. I, the initial product of renin’s action, was itself transformed into Ang. II by an enzyme present in plasma and requiring chloride ion for its activity. This enzymic activity was called “converting enzyme”. Since Ang. I and Ang. II were equally pressor (when injected intravenously into rats), they suggested that the action of converting enzyme was the removal of some groups from Ang. I “leaving that portion of the molecule responsible for its pressor activity unchanged”. The following year Helmer (1955) showed that there was a pharmacological difference between the two forms, Ang. I being inactive and Ang. II active in contracting the rabbit aortic strip. He also showed that plasma would convert the inactive Ang. I to the active Ang. II in vitro, although both forms were equipressor in vivo. Following this suggestion that Ang. II was the true vasoconstrictor and pressor agent, Skeggs et al. (1956) showed that in isolated kidneys perfused with an artificial salt solution, only Ang. II increased perfusion pressure and not Ang. I. From these experiments, they concluded that there was enough converting enzyme (CE) in plasma to transform Ang. I to Ang. II so that, in vivo, the two forms were equipressor, and that the rate-limiting step in the overall formation of Ang. II was the rate of reaction of renin with its substrate.