Angiotensin peptides, metabolism

Chemistry of the renin-angiotensin system. The amino acid sequence of the amino terminal of human angiotensinogen is shown. R denotes the remainder of the protein molecule. See text for additional steps in the formation and metabolism of angiotensin peptides. 

Guillot, F.L. and Audus, K.L. (1990) Angiotensin peptide regulation of fluid-phase endocytosis in brain microvessel endothelial cell monolayers. Journal of Cerebral Blood Flow and Metabolism, 10, 827-834,... 

The great interest devoted to the action of angiotensin is mainly due to the rdle that this peptide could play in the pathogenesis of hypertensive disease. The sites of action of angiotensin are numerous since the peptide mimics the motor actions of either adrenaline or acetylcholine. Such actions are due either to a direct stimulation of the effector cell or to an indirect one by increased activity of the neurovegetative system. Furthermore, angiotensin elicits metabolic and renal effects and stimulates the adrenal medulla. 

ACE not only activates angiotensin but is also involved in the metabolism of other peptides, e.g., it is a major kinin-degrading enzyme. Therefore, ACE inhibitors also increase kinin concentrations. Furthermore, it has recently been shown that these drugs potentiate kinin effects by modulating a direct interaction between the ACE protein and the kinin B2 receptor, which is independent from the enzymatic activity of ACE. Kinin potentiation may be involved in the beneficial action of ACE inhibition since kinins are known to exert cardio- and renoprotective actions. 

Berellini G, Cruciani G, Mannhold R. Pharmacophore, drug metabolism, and pharmacokinetics models on non-peptide ATi, AT2, and AT1/AT2 angiotensin II receptor antagonists. J Med Chem 2005 48 4389-99. 

Metabolism of angiotensinogen by renin produces the decapeptide angiotensin I. This relatively inactive peptide is acted on by a dipeptidase-converting enzyme to produce the very active octapeptide angiotensin II. In addition to converting enzyme, angiotensin I can be acted on by prolyl endopeptidase, an enzyme that removes the first amino acid to form angiotensin 1-7, a peptide primarily active in the brain. ACE has been... 

Omapatrilat Decreases metabolism of natriuretic peptides and formation of angiotensin II Vasodilation increased sodium and water excretion Hypertension heart failure1... 

ACE is therefore a key enzyme for the regulation of blood pressure. Inhibition of this enzyme leads at the same time to a decreased conversion of angiotensin and a decreased degradation of bradykinin. However, ACE has stUl more functions. It is also involved in the metabolism of a whole range of other endogenous peptides, for example endorphins (cf. Opiates - section 5.3). [5]... 

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