We see then the reasons that uncatalyzed reactions of

Info icon This preview shows pages 282–284. Sign up to view the full content.

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 oxy- genase enzymes, to direct the reactions and make them highly specific. It is instructive to consider (1) how these metalloenzymes function to lower the ki- netic barriers to dioxygen reactivity, and (2) how the oxygenase enzymes redi- rect 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 bar- riers to dioxygen reduction by binding dioxygen to two paramagnetic metal ions at the dioxygen binding site, thus overcoming the spin restriction, and by reduc- ing 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 dioxygen- ases, 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 or- ganic 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 hy- droxyl radical. Unlike a free hydroxyl radical, however, which would be highly reactive but nonselective, the reaction that occurs at the active site of cyto- chrome PASO can be highly selective and stereospecific, because the highly re- active 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. III DIOXYGEN TOXICITY A. Background Before we consider the enzymatically controlled reactions of dioxygen in living systems, it is instructive to consider the uncontrolled and deleterious reactions that must also occur in aerobic organisms. Life originally appeared on Earth at a time when the atmosphere contained only low concentrations of dioxygen, and was reducing rather than oxidizing, as it is today. With the appearance of photosynthetic organisms approximately 2.5 billion years ago, however, the
Image of page 282

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

III. DIOXYGEN TOXICITY 261 conversion to an aerobic, oxidizing atmosphere exposed the existing anaerobic organisms to a gradually increasing level of oxidative stress.
Image of page 283
Image of page 284
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern