Angiotensinogen cleavage

The pathway for the formation and metabolism of angiotensin II (Ang II) is summarized in Figure 17-1. The principal steps include enzymatic cleavage of angiotensin I (Ang I) from angiotensinogen by renin, conversion of Ang I to Ang II by converting enzyme, and degradation of Ang II by several peptidases. 

Angiotensinogen, which is secreted by the liver and circulates in the blood, is converted to the physiologically inactive decapeptide angiotensin I by cleavage of a Leu-Leu peptide bond by the 328-residue renin.d f Its precursor preprorenin is produced in the kidneys by the juxtaglomerular cells as well as in some other tissues and undergoes several... 

The EMEA filing for aliskiren contained safety information obtained from a large number of clinical studies in a total of 11,566 treated patients. Aliskiren showed a favorable overall adverse event profile (37.7%) compared to placebo (40.2%). Diarrhea was the most common adverse event and was more common in the aliskiren group (2.4%) versus placebo (1.2%). Relative to ACE inhibitors, which are associated with cough due to inhibition of ACE-dependent bradykinin cleavage, aliskiren demonstrated a significantly improved profile (1.0% vs 3.8% for ACE inhibitors), as expected based on the specificity of renin for angiotensinogen.9... 

Fig. 12. Stepwise enzymatic cleavage of human angiotensinogen X = peptide fragment of angiotensinogen...

Renin is an enzyme of the hydrolase class that catalyzes cleavage of the leucine-leucine bond in angiotensinogen to generate angiotensin I. The enzyme is synthesized as inactive prorenin in the kidney and released into the blood in the active form in response to various metabolic stimuli. The importance of renin in the maintenance of systemic blood pressure was discussed previously (see Juxtaglomerular Apparatus). 

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