Angiotensin-converting enzyme (ACE) measurement in human serum using radioinhibitor ligand binding

MK351A, a tyrosyl analogue of enalaprilic acid (MK422) is a potent inhibitor of angiotensin-converting enzyme (ACE). MK351A was radioiodinated with 125I and used to develop a radio inhibitor binding assay for human serum ACE. 125I MK351A associated rapidly and reversibly with human serum ACE (T 1/2 = 1/2 h). Bound 125I MK351A was displaced by an excess of cold MK351A, to give non-specific binding of less than 1%. Scatchard analysis of binding was linear (r = -0.99, n = 6, p less than 0.001), indicating a single class of binding site. ACE was estimated in serum from normal patients and patients with sarcoid by the radio inhibitor binding assay and by enzyme kinetic assay using Hip-His-Leu as substrate. The two methods for ACE estimation correlated closely (r = 0.87, n = 82, p less than 0.001). The radio inhibitor binding assay for human serum ACE is a simple, sensitive and specific assay which utilizes novel assay methodology.