reactive oxygen species
Wednesday 29 October 2003
Definition: Reactive oxygen species (ROS) or free radicals are chemical species that have a single unpaired electron in an outer orbit. They are highly reactive chemical radicals that are generated as products of oxygen degradation.
Normal metabolic processes
The reduction-oxidation reactions that occur during normal metabolic processes. During normal respiration, molecular oxygen is sequentially reduced by the addition of four electrons to generate water.
Rapid bursts of superoxide production occur in activated polymorphonuclear leukocytes during inflammation. This occurs by a precisely controlled reaction in a plasma membrane multiprotein complex that uses NADPH oxidase for the redox reaction. In addition, some intracellular oxidases (such as xanthine oxidase) generate superoxide radicals as a consequence of their activity.
Transition metals such as iron and copper donate or accept free electrons during intracellular reactions and catalyze free radical formation, as in the Fenton reaction (H2O2 + Fe2+ → Fe3+ + OH + OH-).
Because most of the intracellular free iron is in the ferric (Fe3+) state, it must be first reduced to the ferrous (Fe2+) form to participate in the Fenton reaction. This reduction can be enhanced by superoxide, and thus sources of iron and superoxide are required for maximal oxidative cell damage.
Nitric oxide (NO)
Ntric oxide (NO), an important chemical mediator generated by endothelial cells, macrophages, neurons, and other cell types, can act as a free radical and can also be converted to highly reactive peroxynitrite anion (ONOO-) as well as NO2 and NO3-.
superoxide anion radical (O2-)
hydrogen peroxide (H2O2)
hydroxyl ions (OH-)
Accumulation of reactive oxygen species (ROS) is an oxidative stress to which cells respond by activating various defense mechanisms or, finally, by dying. At low levels, however, ROS act as signaling molecules in various intracellular processes.
Autophagy, a process by which eukaryotic cells degrade and recycle macromolecules and organelles, has an important role in the cellular response to oxidative stress.
It has benne suggested a regulatory role for ROS of mitochondrial origin as signaling molecules in autophagy, leading, under different circumstances, to either survival or cell death. There is arelationship between mitochondria and autophagosomes and mitochondria could have an essential role in autophagosome biogenesis.
Energy created by this unstable configuration is released through reactions with adjacent molecules, such as inorganic or organic chemicals-proteins, lipids, carbohydrates-particularly with key molecules in membranes and nucleic acids.
Free radicals initiate autocatalytic reactions, whereby molecules with which they react are themselves converted into free radicals to propagate the chain of damage. For example, ionizing radiation can hydrolyze water into hydroxyl (OH) and hydrogen (H) free radicals. Enzymatic metabolism of exogenous chemicals or drugs: carbon tetrachloride CCl4 can generate CCl3.
Free radicals are ubiquitous in our body and are generated by normal physiological processes, including aerobic metabolism and inflammatory responses, to eliminate invading pathogenic microorganisms.
Because free radicals can also inflict cellular damage, several defences have evolved both to protect our cells from radicals—such as antioxidant scavengers and enzymes—and to repair DNA damage.
Understanding the association between chronic inflammation and cancer provides insights into the molecular mechanisms involved.
Reactive oxygen species from endogenous and environmental sources induce oxidative damage to DNA, and hence pose an enormous threat to the genetic integrity of cells.
ROS and DNA
Active oxygen species in the nucleotide pool of the cell can produce 8-oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate), which can then be incorporated into cellular DNA. Human cells contain enzyme activity that hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing occurrence of mutations caused by misincorporation. This oxidative DNA damage is restored by the base excision repair (BER) pathway that is conserved from bacteria to humans and is initiated by DNA glycosylases, which simply remove the aberrant base from the DNA backbone by hydrolyzing the N-glycosidic bond (monofunctional DNA glycosylase), or further catalyze the incision of a resulting abasic site (bifunctional DNA glycosylase).
ROS, cell death and aging
Evidence from many organisms has shown that the accumulation of reactive oxygen species (ROS) has a detrimental effect on cell well-being. High levels of ROS have been linked to programmed cell death pathways and to ageing. The dynamics of the actin cytoskeleton are involved in the release of ROS from mitochondria and subsequent cell death.
Reactive oxygen species (ROS) have been shown to be toxic but also function as signalling molecules. This biological paradox underlies mechanisms that are important for the integrity and fitness of living organisms and their ageing.
The pathways that regulate ROS homeostasis are crucial for mitigating the toxicity of ROS and provide strong evidence about specificity in ROS signalling. By taking advantage of the chemistry of ROS, highly specific mechanisms have evolved that form the basis of oxidant scavenging and ROS signalling systems.
free radicals and aging
free radicals and cancer
interaction between nitric oxide and p53
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