Sandbox Reserved 714: Difference between revisions

Line 47:

== Inhibitors ==

As many enzymes, the human soluble epoxide hydrolase can be inhibited by some inhibitors, causing a loss of activity for the enzyme.

The sEH can be inhibited by some metal ions such as Zn2+, Cu2+, Hg2+. It is a noncompetitive inhibition: the metal ion binding to the enzyme reduces its activity without affecting directly the substrate binding, so that the Vmax decreases but the Km remains unchanged. It may be that those metal ions replace the Mg2+ in the N-term active site of the enzyme subunits, which can result in some conformation changes, but this is only an hypothesis.

However, there are also some chemical inhibitors that inhibit the sEH. They are 1-3 disubstitued ureas, carbamates and amides, which are stable inhibitors for the sEH.

Those chemical inhibitors are competitive inhibitors, which can bind in the active site of the enzyme in place of the right substrate, which graphically can be noticed by a Km increase, whereas the Vmax remains unchanged. In fact, according to crystal structures, urea can set up hydrogen bonds and salt bridges with some residues of the sEH active site, which ends up in an “enzyme-substrate”-like complex. Nevertheless, it is also important to notice that those inhibitor must have hydrophobic sidechains in order to fit in the hydrophobic zone of the catalytic site.

</StructureSection>

Sandbox Reserved 714: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 47: / Line 47: @@
 == Inhibitors ==
+As many enzymes, the human soluble epoxide hydrolase can be inhibited by some inhibitors, causing a loss of activity for the enzyme.
+The sEH can be inhibited by some metal ions such as Zn<sup>2+</sup>, Cu<sup>2+</sup>, Hg<sup>2+</sup>. It is a noncompetitive inhibition: the metal ion binding to the enzyme reduces its activity without affecting directly the substrate binding, so that the V<sub>max</sub> decreases but the K<sub>m</sub> remains unchanged. It may be that those metal ions replace the Mg<sup>2+</sup> in the N-term active site of the enzyme subunits, which can result in some conformation changes, but this is only an hypothesis.
+However, there are also some chemical inhibitors that inhibit the sEH. They are 1-3 disubstitued ureas, carbamates and amides, which are stable inhibitors for the sEH.
+Those chemical inhibitors are competitive inhibitors, which can bind in the active site of the enzyme in place of the right substrate, which graphically can be noticed by a K<sub>m</sub> increase, whereas the V<sub>max</sub> remains unchanged. In fact, according to crystal structures, urea can set up hydrogen bonds and salt bridges with some residues of the sEH active site, which ends up in an “enzyme-substrate”-like complex. Nevertheless, it is also important to notice that those inhibitor must have hydrophobic sidechains in order to fit in the hydrophobic zone of the catalytic site.
 </StructureSection>