Lecture {L} Summary

Cytochrome oxidase (Complex IV) activity

The end game of electron transport is the reduction of molecular oxygen to water. The high reduction potential of oxygen provides a strong driving force. Four electrons are required for this reduction, and they are supplied by the input of four molecules of reduced cytochrome c, according to the following equation:

Note that the four protons required for formation of two water molecules are taken up from the matrix, thus contributing to the generation of a transmembrane proton gradient.

This reduction of oxygen is accompanied by proton pumping. Four protons are pumped from the matrix to the cytosolic side yielding the net equation shown in the text (BTS, top of p.506). Protons that are pumped from one side of a membrane to the other, and thus appear in a one-to-one correspondence on both sides of an equation, are sometimes referred to as vectorial protons. Protons appearing on only one side of an equation (such as the one shown above) are referred to as chemical or scalar protons.

Reactive oxygen species

Although the choreography of oxygen reduction in Complex IV is tightly and precisely orchestrated so as to minimize the possibility of release of intermediate oxygen species, occasionally and inevitably a partially reduced oxygen species is produced.

"...danger lurks in the reduction of O₂."

This dire warning appears in our text (BTS, p.506. top). What are ROS and why are they so dangerous to cells? Let's summarize these species and their oxidation states, which are intermediate between the relatively benign molecular oxygen and water:

Superoxide dismutase (SOD): Scavenging free radicals

Given the dangers posed by production of reactive oxygen species, it is not surprising that cells performing oxidative metabolism have also evolved protective mechanisms to protect against oxidative damage. A prime player in the defense is the enzyme superoxide dismutase [SOD, EC 1.15.1.1], which catalyzes the conversion of the superoxide radical/anion to hydrogen peroxide.

Electron transfer

The following are some key points about electron transfer in biological systems:

• Electron transfers are facile
• Electrons can be transferred over distance
• Electron transfer "through space" (QM tunneling)
• Electron transfer through bonds is much more efficient
• Rates within proteins vary with distance between donor and acceptor (dropping ~10-fold per 1.7 Å increase)

Study questions

• Sketch the graph of rate of the free energy dependence of electron transfer rate. Describe the meaning of the term "inverted region"

Page updated 01-06-07

References

1. Berg, Tymoczko, and Stryer. Biochemistry (BTS): 6th edition (2007, Freeman) Ch.18, pp.512-520.
2. Michel H, Behr J, Harrenga A, Kannt A. (1998). Cytochrome c oxidase: Structure and spectroscopy. Ann Rev Biophys Biomol Struct 27: 329-356.
3. Yankovskaya Y, et al. (2003). Architecture of Succinate Dehydrogenase and Reactive Oxygen Species Generation. Science 299: 700-704.