Modeling of Angiotensin Peptide Metabolism in Renal Proximal Tubules

The recent discovery of angiotensin converting enzyme 2 (ACE2) as a functional peptidase within the renin-angiotensin system (RAS) has added a new layer of complexity to the enzymatic cascade of this hormonal system. ACE2 is highly expressed in the proximal tubules of the kidney, an important tissue site involved in blood pressure regulation. Therefore, we derived a model for the processing of Ang I which is the immediate precursor to the biologically active peptides Ang II and Ang-(1-7) based on metabolism data in isolated proximal tubules of the sheep kidney (1). Given the individual experimental velocities for several peptidases expressed in the proximal tubules including ACE, ACE2 and neprilysin, rate constants were calculated to describe the conservation equations for the processing of Ang I, Ang II and Ang-(1-7) We modeled the system with Ang I as the initial substrate and peptide concentrations for the downstream products were calculated using Euler’s method.