Comparison of hydrolysis of atriopeptin II stand‐in substrate by atrial dipeptidyl carboxyhydrolase and angiotension I‐converting enzyme

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Abstract
A new membrane-bound metallo dipeptidyl dipeptidase from bovine atrial tissue homogenates was partially purified. This enzyme was capable of cleaving the dipeptide, phenylalanyl-arginine from the C-terminus of atriopeptin II to give atriopeptin I. The atriopeptins are 2 atrial natriuretic peptides and the existence of the atrial peptide system has implicated the mammalin heart as an endocrine organ. The tetrapeptide benzoyl-glycyl-seryl-phenylalanyl-arginine was synthesized because it contains the C-terminal tripeptide sequence of atriopeptin II and should be useful to test the roles of the atrial enzyme and angiotensin I-converting enzyme in processing the atrial peptides. For the atrial enzyme, Vmax was 13-fold higher and Km 7-fold lower for this stand-in substrate than for benzoyl-glycyl-histidyl-leucine, a standard substrate used to measure converting enzyme activity. The ratio of Vmax/Km as a measure of substrate specificity indicates that the stand-in substrate is 86-fold better than benzoyl-glycyl-histidyl-leucine. In contrast, the stand-in substrate is a 20-fold poorer substrate for the converting enzyme than benzoyl-glycyl-histidyl-leucine. With the stand-in substrate, the converting enzyme showed pronounced substrate inhibition. An effective Vmax and Km were calculated using only concentrations of S below the optimum substrate concentration. The atrial enzyme is distinct from the converting enzyme. The conversion of atriopeptin II to atriopeptin I is a physiological process that is mediated by this enzyme.