Sandbox Reserved 322: Difference between revisions
Brian Huang (talk | contribs) No edit summary |
Brian Huang (talk | contribs) No edit summary |
||
| Line 14: | Line 14: | ||
==='''Structure and Function'''=== | ==='''Structure and Function'''=== | ||
---- | ---- | ||
[[Image:Arginine.jpg|thumb|right|300px|Figure 2: General reaction of arginase hydrolyzing L-arginine to urea and L-ornithine.]] | [[Image:Arginine.jpg|thumb|right|300px|Figure 2: General reaction of arginase hydrolyzing L-arginine to urea and L-ornithine adopted from Christianson<ref name="c"/>.]] | ||
In general arginase is a homotrimeric enzyme, which is present in the fifth and final step of the urea cycle for mammals. In humans, hAI converts L-arginine into L-orinithine and urea as shown in figure 2. Human arginase II plays a role in L-arginine homeostasis, by regulating L-arginine concentrations from cellular biosynthetic reactions such as nitric oxide (NO) biosynthesis<ref name="c"/>. Additionally ''Plasmodium falciparum'' arginase is comparable to human arginase, due to the fact that it is 27% identical with human aginase I and II<ref name="b"/>. | In general arginase is a homotrimeric enzyme, which is present in the fifth and final step of the urea cycle for mammals. In humans, hAI converts L-arginine into L-orinithine and urea as shown in figure 2. Human arginase II plays a role in L-arginine homeostasis, by regulating L-arginine concentrations from cellular biosynthetic reactions such as nitric oxide (NO) biosynthesis<ref name="c"/>. Additionally ''Plasmodium falciparum'' arginase is comparable to human arginase, due to the fact that it is 27% identical with human aginase I and II<ref name="b"/>. | ||
| Line 24: | Line 24: | ||
==='''Mechanism'''=== | ==='''Mechanism'''=== | ||
---- | ---- | ||
[[Image:Mechanism_of_arginase.jpg|thumb|right|300px|Figure 3: Proposed mechanism of arginase hydrolyzing L-arginine to urea and L-ornithine adopted from Kanyo and colleagues.]] | [[Image:Mechanism_of_arginase.jpg|thumb|right|300px|Figure 3: Proposed mechanism of arginase hydrolyzing L-arginine to urea and L-ornithine adopted from Kanyo and colleagues<ref name="d"/>.]] | ||
In general arginase is known to convert L-arginine into urea and L-ornithine, via hydrolysis, the proposed mechanism is adopted from Kanyo and colleagues as shown in figure 3<ref name="d"/>. In the first step of the hydrolytic mechanism, Asp 220 stabilizes the metal-bridging hydroxide ion with a hydrogen bond during a nucleophilic attack at the guanidinium carbon of arginine<ref name="b"/><ref name="d"/>. The resulting tetrahedral intermediate fall apart once a proton is transferred to the amino group of ornithine, and the proton transfer is mediated by Asp 220<ref name="b"/><ref name="d"/>. It is proposed that His 233 shuttles a proton from bulk solvent to the ε-amino group of ornithine before production dissociation<ref name="b"/><ref name="d"/>. Before product dissociation, a water molecule displaces urea<ref name="d"/>. In addition, the metal coordination facilitates the ionization of this water molecule to regenerate a nucleophilic hydroxide ion<ref name="d"/>. Here, proton transfer to bulk solvent may again be mediated by shuttle-group His 233<ref name="b"/><ref name="d"/>. | In general arginase is known to convert L-arginine into urea and L-ornithine, via hydrolysis, the proposed mechanism is adopted from Kanyo and colleagues as shown in figure 3<ref name="d"/>. In the first step of the hydrolytic mechanism, Asp 220 stabilizes the metal-bridging hydroxide ion with a hydrogen bond during a nucleophilic attack at the guanidinium carbon of arginine<ref name="b"/><ref name="d"/>. The resulting tetrahedral intermediate fall apart once a proton is transferred to the amino group of ornithine, and the proton transfer is mediated by Asp 220<ref name="b"/><ref name="d"/>. It is proposed that His 233 shuttles a proton from bulk solvent to the ε-amino group of ornithine before production dissociation<ref name="b"/><ref name="d"/>. Before product dissociation, a water molecule displaces urea<ref name="d"/>. In addition, the metal coordination facilitates the ionization of this water molecule to regenerate a nucleophilic hydroxide ion<ref name="d"/>. Here, proton transfer to bulk solvent may again be mediated by shuttle-group His 233<ref name="b"/><ref name="d"/>. | ||