Reactive Oxygen Species Flashcards
Free Radical
Molecule that has a single unpaired electron in an orbital and is highly reactive. Are scavenged by antioxidants.
What are examples of free radicals?
Superoxide, hydroxyl radical, nitric oxide, nitrogen dioxide
What molecules can lead to free radicals?
Hydrogen peroxide and peroxynitrite
What can enhance ROS formation?
High oxygen tension (supplemental oxygen for COPD), hypoxia, carbon monoxide poisoning, ischemic reperfusion, high levels of acetaldehyde from alcohol abuse
How is superoxide formed in the Electron transport chain?
The one electron reduced from CoQH is free in the membrane and can accidentally transfer an electron to dissolved oxygen, forming superoxide
Why is mitochondrial DNA more susceptible to ROS damage than nuclear DNA?
It does not have histones, and is close to CoQ
When is superoxide (anion radical) formed?
In the mitochondria during the ETC (coQ), in the cytosol by microsomal cytochromes P450, and in peroxisomes by cytochromes P450
Superoxide Dismutase (SOD)
Used two superoxides at the same time as substrates (very efficient and fast).
Where can you find superoxide dismustase?
Extracellular (copper), cytosol (copper and zinc),and mitochondria (manganese) and
Hydrogen Peroxide is formed…
In SOD catalyzed reactions, xanthine oxidase catalyzed reactions, B-oxidation of very long chain fatty acids in peroxisomes.
When hydrogen peroxide is not salvaged it…
Diffuses through membranes and leads to hydroxyl radicals in Haber-Weiss and Fenton reactions
How is hydroxyl radical (OH-) formed?
Non-ezymatically formed from hydrogen peroxide when it acts with superoxide or ferrous ions
What can scavenge hydrogen peroxide?
Catalase or glutathione peroxidase
Catalase
Found mainly in peroxisomes and used hydrogen peroxide for detoxification of toxins. Contains heme and binds two hydrogen peroxides and substrates at the same time
Glutathione Peroxidase
Can scavenge hydrogen peroxide. Needs two reduced glutathione molecules (2 GSH) to act on hydrogen peroxide. Uses selenium as a cofactor.
What does a crushing injury lead to?
Hydroxyl radicals due to the loss of sequestration of iron
What are some nonenzymatic endogenous radical scavengers?
Uric acid (can lead to gout) is half of the scavengers found in blood and lungs. Glutathione. Bilirubin (could lead to jaundice)
What are some examples of dietary radical scavengers?
Vitamins, PUFAs, carotenoids, flavonoids, phytochemicals, polyphenols, isoprenoids, and reservatol.
Amyotrophic Lateral Sclerosis (ALS)
Lou Gherigs. Caused by a deficiency of superoxide dismustase (SOD). Mostly idiopathic, but can be a genetic defect. Degenerative disease of the upper ad lower motor neurons that control voluntary muscle movement. Leads to difficulty breathing (vocal cord dysfunction), head drop, muscle weakness. Onset after 40-50 years of age
NADPH oxidase
Used NADPH and molecular oxygen to form superoxide. Used in phagocytic cells. Found in the cell membrane of neutrophils. Generates superoxide for respiratory burst.
Myeloperoxidase
Uses hydrogen peroxide and chloride ions to form hypochlorous acid (bleach). Used in phagocytic cells, secreted into the phagolysosome. Leads to the coloration of pus, due to two heme link groups
Inducible nitric oxide synthase
Used NADPH and arginine to from nitric oxide and citrulline
Physiological Functions of Nitric Oxide
Relaxes smooth muscle, prevents platelet aggregations, functions as a neurotransmitter in the brain. Formed in macrophages by inducible NO synthase.
Chronic Granulomatous Disease (CGD)
Granulomas contain sequestered bacteria in infected cells. Recurrent severe infections by bacteria (pneumonia) or fungi (aspergillus). Mostly X-linked. Hereditary NADPH oxidase deficiency.
Myeloperoxidase Deficiency
Recurrent severe infections by Candida albicans caused by decreased formation of HOCL (bleach). Bacteria are still destroyed by hydroxyl radicals and peroxynitrate as superoxide and nitric oxide can be formed. Results in oral and genital infections, and sometimes, systemic infections.
