Sandbox Reserved 489: Difference between revisions
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Renin secretion is stimulated by a decrease in arterial blood pressure, a decrease in sodium chloride levels in kidney [http://en.wikipedia.org/wiki/Nephron nephrons], or [http://en.wikipedia.org/wiki/Sympathetic_nervous_system sympathetic nervous system] activity. | Renin secretion is stimulated by a decrease in arterial blood pressure, a decrease in sodium chloride levels in kidney [http://en.wikipedia.org/wiki/Nephron nephrons], or [http://en.wikipedia.org/wiki/Sympathetic_nervous_system sympathetic nervous system] activity. | ||
The substrate of renin, angiotensinogen, is a 452 amino acid residue in humans. Renin utilizes two aspartate residues in the <scene name='Sandbox_Reserved_489/Activesiteasps2/2'>active site</scene> to cleave the peptide bond between leucine and valine residues on angiotensinogen. Angiotensin I is an inactive short peptide of 10 amino acids that is produced by the renin cleavage reaction. The two aspartate residues | The substrate of renin, angiotensinogen, is a 452 amino acid residue in humans. Renin utilizes two aspartate residues in the <scene name='Sandbox_Reserved_489/Activesiteasps2/2'>active site</scene> to cleave the peptide bond between leucine and valine residues on angiotensinogen. Angiotensin I is an inactive short peptide of 10 amino acids that is produced by the renin cleavage reaction. The close proximity of the two aspartate allows the acid-base hydrolysis mechanism to cleave the peptide bond. Because the aspartate residues are close together one is slightly acidic and the other is slightly basic. The mechanism of the catalysis is an acid-base transfer of water between the two aspartate residues. There is a water molecule associated with the two aspartate residues in the active site and also a water associated with the peptide bond that is cleaved. Initially one aspartate residue carbonyl is deprotonated and the other is protonated. The deprotonated aspartate removes a proton from water allowing the water to attack the carbonyl of the peptide bond in the substrate forming a tetrahedral oxyanion intermediate on the substrate. Rearrangement of the intermediate causes protonation of the amide on the substrate completing the cleavage reaction. A concerted mechanism of action has also been proposed that states the attack of the carbonyl group and protonation of the amide group in a single step with no covalent intermediate. | ||
Renin can also bind the renin receptor [http://en.wikipedia.org/wiki/ATP6AP2 ATPase H(+)-transporting lysosomal accessory protein 2] (ATP6AP2) to convert angiotensinogen to angiotensin I at a much faster rate.<ref>PMID: 12045255</ref> | Renin can also bind the renin receptor [http://en.wikipedia.org/wiki/ATP6AP2 ATPase H(+)-transporting lysosomal accessory protein 2] (ATP6AP2) to convert angiotensinogen to angiotensin I at a much faster rate.<ref>PMID: 12045255</ref> | ||
