BIOCHEMISTRY OF FREE-RADICALS - FROM ELECTRONS TO TISSUES

Free radicals are chemical species with an unpaired electron in the ou ter valence orbitals. The unpaired electron makes them paramagnetic (p hysics) and relatively reactive (chemistry). The free radicals that ar e normal metabolites in aerobic biological systems have varied reactiv ities, ranging from the high reactivity of hydroxyl radical (t(1/2) = 10(-9) s) to the low reactivity of melanins (t(1/2) = days). The univa lent reduction of oxygen that takes place in mammalian organs produces superoxide radicals at a rate of about 2% of the total oxygen uptake. The primary production of superoxide radicals sustains a free radical chain reaction involving a series of reactive oxygen species (hydroge n peroxide, hydroxyl and peroxyl radical and singlet oxygen). Nitric o xide is almost unreactive as free radical except for its termination r eaction with superoxide radical to yield the strong oxidant peroxynitr ite. Nitric oxide also reacts with ubiquinol in a redox reaction, with cytochrome oxidase competitively with oxygen, and oxymyoglobin and ox yhemoglobin displacing oxygen. Septic shock and endotoxemia produce mu scle dysfunction and oxidative stress due to increased steady state co ncentrations of reactive oxygen and nitrogen species.