Free radicals

Cells generate energy by reducing molecular oxygen to water and small amounts of reduced reactive oxygen forms are produced by mitochondrial respiration, and some of these forms are free radicals.

Chemical species with a single unpaired electron in the outer orbit which creates energy because of its unstable configuration that is released via reactions with adjacent molecules in proteins, lipids and carbohydrates with special reactions with membranes and nucleic acids.

May damage lipids, proteins, and nucleic acids.

Can cause peroxidation of lipids and DNA damage and contribute to cardiovascular disease and cancer.

Ref2242ed to as reactive oxygen species.

Usually kept in homeostasis by scavenger antioxidant systems including superoxide dismutase, thioredoxin, and glutaredoxin.

Interaction with DNA and mitochondrial DNA can result in gene mutations altering electron transport chains and resulting in tumor progression.

Cancer transformed cells generate higher levels of reactive oxygen species contributing to proliferation and angiogenesis.

Epidermal growth factor receptor pathway and platelet derived growth factor receptor pathway utilize free radicals as signaling intermediates and they can inactivate the tumor suppressor gene PTEN.

Increased intracellular levels can prolong stabilization of oxygen sensitive hypoxia inducible factor 1 alpha, allowing translocation to the nucleus and promotion of hypoxic genes which stimulate angiogenesis.

Have a role in the initiation of cancer via effects on DNA damage resulting in mutations, activations of oncogenes and loss of tumor suppressor gene function.

Reactive oxygen species have a role in the activation of c-myc oncogene and in the hypoxia inducible factor (HIF)-1 transcription factor, both of which drive cell growth and proliferation.

Interaction with DNA and mitochondrial DNA can result in gene mutations altering electron transport chains and resulting in tumor progression.

Cells have defense scavenging systems to prevent an imbalance between free radical production that can result in oxidative stress which is associated with cell injury.

Injury can manifest itself as chemical, radiation, ischemic and reperfusion type as well as affect cellular aging and bacterial killing by phagocytes.

Can initiate autocatalytic reactions where molecules they react with can be converted to free radicals and propagate damage.

Can be initiated within cells by the absorption of radiant energy from ultraviolet light and x-ray exposure, by enzymatic metabolism of chemical or drug exposure, by reduction-oxidation reactions that occur during normal metabolic processes, by transition metals iron, and copper as they donate or accept free electrons during intracellular reactions and catalyze free radical formation, and Nitric oxide that can act as a free radical and can be converted to highly reactive anions.

may cause peroxidation of lipids within plasma and organ membranes.

Oxidative damage occurs when double bonds in unsaturated fatty acids of membrane lipids are attacked by oxygen derived free radicals.

Lipid free radical interactions yield peroxides which are unstable and reactive and causes autocatalytic reactions, propagation, resulting in membrane and cell damage.

Results in protein fragmentation by oxidizing amino acid residue side chains, promote protein-protein cross linkages and oxidize protein backbone.

React with thymidine in DNA of nuclear and mitochondria producing single stranded breaks.

While they are unstable and decay spontaneously there are several nonenzymatic and enzymatic systems contributing the inactivation of free radicals.

Antioxidants., including vitamins E, A, C and glutathione block the initiation of or inactivate free radicals.

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