Superoxide from multiple cellular sources is dismutated by SOD to H2O2, then neutralized by catalase and glutathione peroxidase, with NADPH from the pentose phosphate pathway regenerating the system.
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ROS Antioxidant Defense System
Reactive oxygen species (ROS) are unavoidable byproducts of aerobic metabolism. Superoxide (O2-) is the primary product, generated by electron leakage from Complex I and III of the ETC, NADPH oxidase (NOX) in immune cells and vascular tissue, and xanthine oxidase. At low concentrations, ROS serve as signaling molecules. Above a threshold, they cause oxidative damage to DNA, lipids, and proteins.
The antioxidant defense system is tiered and enzymatic, not a passive free-radical scavenger.
Superoxide dismutase (SOD1 cytosolic, SOD2 mitochondrial, SOD3 extracellular) converts O2- to H2O2. H2O2 is handled by two parallel enzymes: catalase (in peroxisomes, high-capacity at high H2O2) and glutathione peroxidase (GPx, mitochondria and cytosol, lower-capacity but handles lipid hydroperoxides).
GPx requires reduced glutathione (GSH) as a cofactor, oxidizing it to GSSG. Glutathione reductase (GR) regenerates GSH from GSSG using NADPH. NADPH is produced primarily by glucose-6-phosphate dehydrogenase (G6PD) in the pentose phosphate pathway, creating an indirect link between glucose metabolism and antioxidant capacity.
Nrf2, the master antioxidant transcription factor, upregulates GPx, GR, thioredoxin reductase, heme oxygenase-1, and G6PD in response to oxidative stress.
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Source & accuracy
This ros antioxidant defense system is an editorial illustration built to represent the concept accurately. Where it shows figures, they are typical or representative values chosen to make the relationship clear, not a single underlying dataset. The diagram and its explainer are reviewed and maintained centrally, and updated over time as understanding improves.
A relay that defuses reactive oxygen step by step
Cells continuously generate reactive oxygen species (ROS), partly as a byproduct of mitochondrial energy production and partly on purpose for signaling and microbial killing. The antioxidant defense system neutralizes them in a sequence. Superoxide dismutase (SOD) first converts superoxide into hydrogen peroxide, which is still reactive but more manageable.
Hydrogen peroxide is then broken down to water by catalase and by glutathione peroxidase. This stepwise hand-off avoids letting the most damaging intermediates accumulate.
Why NADPH keeps the system running
Glutathione peroxidase consumes reduced glutathione as it neutralizes peroxide. To keep working, that glutathione must be regenerated, a job done by an enzyme that draws reducing power from NADPH. The pentose phosphate pathway is a major source of this NADPH, which is why redox defense is tied to cellular metabolism.
Antioxidant capacity is a regulated network, not a single substance, which is one reason high-dose antioxidant supplements do not straightforwardly improve health and can sometimes blunt useful adaptive signaling. This is general educational information, not medical advice; supplement choices should involve a qualified professional.
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