We see then the reasons that uncatalyzed reactions of dioxygen are usually either slow or unselective. The functions of the metalloenzymes for which dioxygen is a substrate are, therefore, to overcome the kinetic barriers imposed by spin restrictions or unfavorable one-electron reduction pathways, and, for the oxygenase
enzymes, to direct the reactions and make them highly specific. It is instructive to consider (1) how these metalloenzymes function to lower the kinetic barriers to dioxygen reactivity, and (2) how the oxygenase enzymes redirect the reactions along different pathways so that very different products are obtained. The first example given below is cytochrome c oxidase. This enzyme catalyzes the four-electron reduction of dioxygen. It overcomes the kinetic barriers to dioxygen reduction by binding dioxygen to two paramagnetic metal ions at the dioxygen binding site, thus overcoming the spin restriction, and by reducing dioxygen in a two-electron step to peroxide, thus bypassing the unfavorable one-electron reduction to form free superoxide. The reaction occurs in a very controlled fashion, so that the energy released by dioxygen reduction can be used to produce ATP. A second example is provided by the catechol dioxygenases, which appear to represent substrate rather than dioxygen activation, and in which dioxygen seems to react with the substrate while it is complexed to the paramagnetic iron center. Another example given below is the monooxygenase enzyme cytochrome PASO, which catalyzes the reaction of dioxygen with organic substrates. It binds dioxygen at the paramagnetic metal ion at its active site, thus overcoming the spin restriction, and then carries out what can be formally described as a multielectron reduction of dioxygen to give a highly reactive high-valent metal-oxo species that has reactivity like that of the hydroxyl radical. Unlike a free hydroxyl radical, however, which would be highly reactive but nonselective, the reaction that occurs at the active site of cytochrome PASO can be highly selective and stereospecific, because the highly reactive metal-oxo moiety is generated close to a substrate that is bound to the enzyme in such a way that it directs the reactive oxygen atom to the correct position. Thus, metalloenzymes have evolved to bind dioxygen and to increase while controlling its reactivity.
enzymes, to direct the reactions and make them highly specific. It is instructive to consider (1) how these metalloenzymes function to lower the kinetic barriers to dioxygen reactivity, and (2) how the oxygenase enzymes redirect the reactions along different pathways so that very different products are obtained. The first example given below is cytochrome c oxidase. This enzyme catalyzes the four-electron reduction of dioxygen. It overcomes the kinetic barriers to dioxygen reduction by binding dioxygen to two paramagnetic metal ions at the dioxygen binding site, thus overcoming the spin restriction, and by reducing dioxygen in a two-electron step to peroxide, thus bypassing the unfavorable one-electron reduction to form free superoxide. The reaction occurs in a very controlled fashion, so that the energy released by dioxygen reduction can be used to produce ATP. A second example is provided by the catechol dioxygenases, which appear to represent substrate rather than dioxygen activation, and in which dioxygen seems to react with the substrate while it is complexed to the paramagnetic iron center. Another example given below is the monooxygenase enzyme cytochrome PASO, which catalyzes the reaction of dioxygen with organic substrates. It binds dioxygen at the paramagnetic metal ion at its active site, thus overcoming the spin restriction, and then carries out what can be formally described as a multielectron reduction of dioxygen to give a highly reactive high-valent metal-oxo species that has reactivity like that of the hydroxyl radical. Unlike a free hydroxyl radical, however, which would be highly reactive but nonselective, the reaction that occurs at the active site of cytochrome PASO can be highly selective and stereospecific, because the highly reactive metal-oxo moiety is generated close to a substrate that is bound to the enzyme in such a way that it directs the reactive oxygen atom to the correct position. Thus, metalloenzymes have evolved to bind dioxygen and to increase while controlling its reactivity.
Tidak ada komentar:
Posting Komentar