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Glutathione reductase is a very important enzyme
in metabolism. It catalyzes the reduction of
glutathione disulfide (GSSG) to glutathione (GSH),
using NADPH as the electron donor. This
reaction permits GSH to function as an
intracellular reducing agent.
GSSG + NADPH -> 2GSH +
NADP+
The enzyme contains an essential
electron-transfer cofactor, flavin adenine
dinucleotide (FAD). In reality, the reduction
of GSSG is rather complex and proceeds in two
steps:
E + NADPH + H+ ->
EH2 + NADP+
EH2 + GSSG -> E +
2GSH
The proposed mechanism is as follows:
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First Step: E + NADPH +
H+ -> EH2 +
NADP+
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Second Step: EH2 + GSSG
-> E + 2GSH
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Crystallographic analysis has provided snapshots
along this pathway ( PA Karplus & GE Schulz
- J. Mol. Biol. 210, 163-180, 1989;
PDB files = 1GRA, 1GRB, 1GRE, 1GRF, 3GRS).
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This view shows the oxidized enzyme
with FAD (blue), CYS 58 and CYS 63 (CPK)
and TYR 197
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This view shows the reduced enzyme
after reaction with NADPH (magenta). Note
that the TYR has moved
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In this view we see GSSG (green)
bound to the oxidized enzyme.
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In this view we see mixed disulfide
between CYS 58 and GSH (green). One
molecule of GSH (cyan) has been
reduced
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