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BRIAN J. MORRIS, IAN A. REID, A “Renin-Like” Enzymatic Action of Cathepsin D and the Similarity in Subcellular Distributions of “Renin-Like” Activity and Cathepsin D in the Midbrain of Dogs, Endocrinology, Volume 103, Issue 4, 1 October 1978, Pages 1289–1296, https://doi.org/10.1210/endo-103-4-1289
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The proposal that brain “rerun-like” activity may be due not to renin but to an action of brain cathepsin D on angiotensinogen during assay at low pH (ca. 5) was tested using pure bovine cathepsin D with dog and human angiotensinogen from cerebrospinal fluid (CSF) and nephrectomized plasma. Cathepsin D generated angiotensin I from CSF and plasma at a rate directly proportional to the concentration of enzyme added. The rate of hydrolysis of angiotensin I from angiotensinogen was estimated as 0.028%·min-1·g cathepsin D-1 for dog CSF, 0.001 for human CSF, 0.00035 for nephrectomized dog plasma, and 0.00001 for nephrectomized human plasma. Thus, cathepsin D hydrolyzes dog angiotensinogen about 30 times faster than it hydrolyzes human angiotensinogen. The rate of reaction in plasma is about l/100th that in CSF. The subcellular distribution of renin-like activity in the midbrain of dogs was compared with that of cathepsin D and acid phosphatase, both lysosomal enzymes, by differential and isopycnic gradient centrifugation. The distribution of each was similar, with the distributions of renin-like activity and cathepsin D bearing the greatest similarity. Taken together with previous data from this laboratory concerning similarities in enzymatic and physical properties of the latter protease activities, the present results add further support to the proposal that the renin-like activity that has been reported in brain is actually a reaction of brain cathepsin D with angiotensinogen during assay at low pH in vitro to form angiotensin I, the brain being devoid of genuine renin. The present work also provides the first direct evidence for a renin-like hydrolysis of the Leu10-Leu11 bond of angiotensinogen by cathepsin D.
