Biomaterial Database

Is angiotensinogen a renin inhibitor and not the substrate for renin? 1986

K Poulsen, and J Jacobsen

The cleavage of the angiotensinogen molecule by renin is slow. The rate constant for cleavage of the enzyme-substrate complex, Kcat (turnover number) is lower than usual for enzymes (0.6/s for the homologous human renin reactions and 0.15/s for the homologous mouse renin reaction). Thus each round of catalysis occurs in 1.7 s in the human and 6.7 s in the mouse reaction. The Kcat/Km values (10(4)-10(6) l/mol per s; Km, Michaelis constant) are high and in the range for protein inhibitors. The association constants (Ka) are (10(6)-10(7) l/mol) close to that of inhibitors. The slow rate seems to be favourable since homologous reactions are slower than heterologous. Angiotensinogen is structurally related to alpha1-antitrypsin. We conclude that kinetic as well as structural data indicate that angiotensinogen might be considered a protease inhibitor for renin.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D012083	Renin	A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19.	Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000808	Angiotensinogen	An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver in response to lowered blood pressure and secreted into blood circulation. Angiotensinogen is the inactive precursor of the ANGIOTENSINS produced in the body by successive enzyme cleavages. Cleavage of angiotensinogen by RENIN yields the decapeptide ANGIOTENSIN I. Further cleavage of angiotensin I (by ANGIOTENSIN CONVERTING ENZYME) yields the potent vasoconstrictor octapeptide ANGIOTENSIN II; and then, via other enzymes, other angiotensins also involved in the hemodynamic-regulating RENIN-ANGIOTENSIN SYSTEM.	Hypertensinogen,Renin-Substrate,SERPINA8,Proangiotensin,Renin Substrate Tetradecapeptide,Serpin A8,Renin Substrate,Tetradecapeptide, Renin Substrate
D000809	Angiotensins	Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.	Angiotensin
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining