Production of Superoxide
Recent investigations suggest that Complex I is a potent source of reactive oxygen species. Complex I can produce superoxide (as well as hydrogen peroxide), through at least two different pathways. During forward electron transfer, only very small amounts of superoxide are produced (probably less than 0.1% of the overall electron flow).
During reverse electron transfer, Complex I might be the most important site of superoxide production within mitochondria, with up to 5% of electrons being diverted to superoxide formation. Reverse electron transfer, the process by which electrons from the reduced ubiquinol pool (supplied by succinate dehydrogenase, glycerol-3-phosphate dehydrogenase, or dihydro-oorotate dehydrogenase in mammalian mitochondria) pass through Complex I to reduce NAD+ to NADH, driven by the inner mitochondrial membrane potential electric potential. Although it is not precisely known under what pathological conditions reverse-electron transfer would occur in vivo, in vitro experiments indicate that it can be a very potent source of superoxide when succinate concentrations are high and oxaloacetate or malate concentrations are low.
Superoxide is a reactive oxygen species that contributes to cellular oxidative stress and is linked to neuromuscular diseases and aging. NADH dehdyrogenase produces superoxide by transferring one electron from FMNH2 to oxygen (O2). The radical flavin leftover is unstable, and transfers the remaining electron to the iron-sulfur centers. Interestingly, it is the ratio of NADH to NAD+ that determines the rate of superoxide formation.
Read more about this topic: NADH Dehydrogenase
Famous quotes containing the words production of and/or production:
“The growing of food and the growing of children are both vital to the family’s survival.... Who would dare make the judgment that holding your youngest baby on your lap is less important than weeding a few more yards in the maize field? Yet this is the judgment our society makes constantly. Production of autos, canned soup, advertising copy is important. Housework—cleaning, feeding, and caring—is unimportant.”
—Debbie Taylor (20th century)
“From the war of nature, from famine and death, the most exalted object which we are capable of conceiving, namely, the production of the higher animals, directly follows. There is grandeur in this view of life, with its several powers, having been breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.”
—Charles Darwin (1809–1882)