MBMB 451b

Copyright 2000, E.C. Niederhoffer

Sample Problem

Glutathione reductase is an enzyme that is responsible for maintaining the reduced form of glutathione (GSH) in the serum. Briefly explain the key features of this enzyme and the flow of electrons that occurs during the catalytic steps.

Key features:

• bound FAD
• redox-active disulfide
• Tyr that blocks access to FAD
• Glu and His that serve in acid-base catalysis

Catalytic steps:

• 1st stage - E_ox binds NADPH, which reduces FAD_ox, which immediately reduces the redox-active disulfide to thiols

Formation of SH---FAD charge-transfer complex and H-bonding network between Glu-His-Cys.

NADP⁺ is released

• 2nd stage - GSSH binds and forms mixed disulfide with Cys58, assisted by H⁺ abstraction by His.

One GSH released by protonation by His (general acid)

Cys63 attacks mixed disulfide to release 2nd GSH and regenrate redox-active disulfide

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