Figure 1

The schematic of the redox cycle shows the relationship between antioxidant enzymes and glutathione. All enzymes are shown in green, substrates and products in blue, and inhibitors in red. Glutathione (GSH) is synthesized from amino acids by the action of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme, and glutamyl synthase (GS). This reaction requires energy, is ATP-limited and is specifically inhibited at the level of γ-GCS by _L-buthionine-(S,R)-sulfoximine (BSO). GSH undergoes the glutathione-peroxidase (GSH-PX) coupled reaction, thereby detoxifying reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂). A major source of H₂O₂ is the biochemical conversion of superoxide anion (O₂ ^-•) by the action of superoxide dismutase (SOD). During this reaction, GSH is oxidized to generate GSSG, which is recycled back to GSH by the action of glutathione reductase (GSSG-RD) at the expense of reduced nicotinamide (NADPH/H⁺), thus forming the redox cycle. The reduction of the glutathione pathway is blocked by the action of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU). The major source of NADPH/H⁺ comes from the conversion of glucose, a reaction blocked by dehydroepiandrosterone (DHEA).