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 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 residue has a higher pKa and the other residue has a lower pKa. 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 | 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 residue has a higher pKa and the other residue has a lower pKa. 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 active site aspartate and water attack the scissle peptide bond in a single step with no covalent tetrahedral intermediate, but still forms the tetrahedral transition state. | ||
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> | ||
