The Golden Mean of Healthy Living: Redox Equilibrium

Cellular redox balance refers to the dynamic equilibrium between oxidants (reactive oxygen species, ROS) and antioxidants in a cell. This balance is crucial for maintaining proper cellular function and responses. Reactive oxygen species (ROS), including superoxide (O2−), hydrogen peroxide (H2O2), and hydroxyl radical (HO·), are continuously produced as byproducts of normal cellular metabolism. Under excessive stress conditions, cells will produce numerous ROS, and the living organism eventually evolves series of response mechanisms to adapt to the ROS exposure as well as utilize it as a signaling molecule. ROS molecules trigger oxidative stress in a feedback mechanism involving many biological processes, such as apoptosis, necrosis and autophagy.

Growing evidence suggests that ROS play a critical role as a signaling molecule throughout the entire cell death pathway. Overwhelming production of ROS can destroy organelle structures and bio-molecules, leading to an inflammatory response that is known as an underpinning mechanism for the development of diabetes and cancer. Cytochrome P450 enzymes (CYP) are regarded as the markers of oxidative stress and can transform toxic metabolites into ROS which can cause injury of cells. Accordingly, cells have evolved a balanced system to neutralize the extra ROS, namely antioxidant systems that consist of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidases (GPxs), thioredoxin (Trx) as well as supplemental non-enzymatic antioxidants such as vitamins C and E, which play a crucial role in maintaining redox balance by neutralizing or eliminating ROS, collectively reducing oxidative state.

The balance between oxidants and antioxidants is maintained through a delicate interplay of enzyme-catalyzed reactions, such as the glutathione redox cycle, and non-enzymatic thiol-disulfide exchange reactions. Imbalance towards oxidative stress occurs when ROS production exceeds antioxidant capacity, leading to damage of biomolecules, including DNA, proteins, and lipids. Conversely, antioxidant excess can lead to reduced cellular responses to oxidative stress. Cellular redox balance is regulated by transcription factors, such as Nrf2, which responds to oxidative stress by inducing antioxidant and cytoprotective genes. Spatial-temporal regulation of oxidative stress determines cellular fate, with activation of antioxidant and cytoprotective machinery leading to restoration of redox balance.

In summary, cellular redox balance is a dynamic equilibrium between oxidants and antioxidants, essential for maintaining proper cellular function and response. Disruption of this balance can lead to oxidative stress, which can have detrimental effects on cellular health. In our world of excess outer as well as inner stress, supplementation of antioxidants may be essential for maintaining this delicate, but most essential balance.