Catalase, an iron-containing antioxidant enzyme, uses NADPH as a crucial protecting cofactor, preventing its inactivation by hydrogen peroxide (H2O2) through electron donation, thus maintaining its ability to break down (H2O2) into water and oxygen, a vital process for cellular defense against oxidative stress.

Boosting catalase function often involves enhancing its iron center or modifying its NADPH binding site.

Catalase & NADPH Interaction Protection Mechanism: NADPH binds to catalase and donates electrons to prevent the enzyme from forming an inactive intermediate (Compound II) when it reacts with (H2O2).

Redox Cycling: This protection involves NADPH being oxidized to NADP+, with another NADPH molecule then replacing it, creating a cycle that preserves catalase's activity.

Broader Role: This protective action extends beyond just preventing Compound II, suggesting broader roles for NADPH in protecting catalase from oxidative damage. Iron's Role in Catalase Essential Cofactor: Iron is a critical component (cofactor) within the heme group of the catalase enzyme, essential for its catalytic activity.

Catalytic Cycle: The iron center cycles through different states, forming high-valent intermediates (like Compound I) to facilitate the breakdown of (H2O2).

Boosting Catalase Activity & Iron Nanozymes: Researchers design iron-containing nanozymes (SAzymes) where tuning the distance between iron atoms enhances catalase-like activity or selectivity for ROS scavenging.

NADPH Mimics/Inhibitors: Developing specific molecules (like BT-Br) that bind to the NADPH site can either inhibit catalase (for cancer therapy, inducing ferroptosis) or, conversely, stabilize it for therapeutic use.

Structural Modification: Modifying the enzyme's structure to create functional dimers or "wired" systems can improve electron transfer and overall performance, sometimes using iron-containing compounds.

Why it Matters Oxidative Stress: Catalase is a primary antioxidant, and its malfunction is linked to diseases like diabetes, Alzheimer's, and cancer.

Therapeutic Potential: Understanding these interactions allows for strategies to boost catalase for neurodegenerative diseases or inhibit it to fight cancer, often by targeting the iron center or NADPH binding.