reactive oxygen species
Summary
Reactive oxygen species (ROS) are highly reactive molecules derived from oxygen, including superoxide (O2•−), hydrogen peroxide (H2O2), and hydroxyl radical (•OH). They cause cellular injury via lipid peroxidation, protein denaturation, and DNA damage, and are implicated in aging, inflammation, ischemia-reperfusion injury, and carcinogenesis. The body neutralizes ROS using enzymes like superoxide dismutase, catalase, and glutathione peroxidase.
Detail
ROS are generated endogenously as byproducts of oxidative phosphorylation (electron leakage from the mitochondrial electron transport chain), by NADPH oxidase in phagocytes (respiratory burst for microbial killing), by xanthine oxidase, and by ionizing radiation or drug metabolism (e.g., acetaminophen via cytochrome P450). Key species include superoxide anion (O2•−), hydrogen peroxide (H2O2), hydroxyl radical (•OH, the most damaging), and singlet oxygen.
Pathophysiology: ROS damage cells through three main mechanisms: (1) lipid peroxidation of membrane lipids leading to loss of membrane integrity, (2) oxidative modification of proteins causing loss of enzymatic activity and misfolding, and (3) DNA damage including strand breaks and base modifications, which can lead to mutagenesis and carcinogenesis.
Clinical relevance: ROS play a central role in ischemia-reperfusion injury (reoxygenation after ischemia generates a burst of ROS causing further tissue damage, seen in MI, stroke, and organ transplantation), chronic granulomatous disease (defective NADPH oxidase impairs ROS-mediated killing of catalase-positive organisms), acetaminophen toxicity (NAPQI depletes glutathione, allowing ROS accumulation and hepatocyte necrosis), atherosclerosis (oxidized LDL uptake by macrophages forming foam cells), aging (mitochondrial theory of aging), neurodegenerative diseases (Parkinson's, Alzheimer's), and radiation injury (ionizing radiation generates hydroxyl radicals from water hydrolysis).
Antioxidant defenses: Superoxide dismutase (SOD) converts superoxide to H2O2; catalase and glutathione peroxidase convert H2O2 to water; vitamin E, vitamin C, and glutathione act as free radical scavengers. Understanding these defense pathways is important for USMLE questions regarding chronic granulomatous disease workup (nitroblue tetrazolium test) and antioxidant vitamin functions.
Sources
- Robbins Basic Pathology, 10th ed.
- First Aid for the USMLE Step 1
- Kumar & Clark's Clinical Medicine
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.