Principles of Biochemistry, Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Electron Transfer, Oxidative Phosphorylation, and Regulation of ATP Synthesis
Cytochromes are hemoproteins that mediate electron transfer

Cytochromes are iron-containing Proteins with a characteristic red or brown color. Operating in a specific sequence, they transfer electrons from ubiquinone to molecular oxygen. Cytochromes belong to the Class of Hemoproteins, whose molecules contain iron bound to an iron-porphyrin group, or heme, which is structurally similar to the prosthetic group of Hemoglobin (Fig. 10-26). Although cytochromes were discovered long ago (initially named histohematins), it was not until 1925 that David Keilin established that the function of these compounds is intimately linked to Biological Oxidation. Using a spectroscope, he detected red-brown pigments in the flight Muscles of living insects. He observed that THE SPECTRUM OF these pigments changed noticeably when an insect, secured to a Microscope slide, made sharp movements in an attempt to escape. Keilin named these pigments cytochromes and hypothesized that they transfer electrons from nutrient substances to oxygen, undergoing reversible Oxidation and reduction in the process. There are three classes of cytochromes—a, b, and c—distinguished by their absorption spectra. In its reduced (ferrous) form, each cytochrome exhibits three distinct absorption bands in the visible region of the spectrum (Fig. 17-11). Keilin demonstrated that cytochromes act in a definite sequence and that the final cytochrome in this chain transfers electrons to oxygen.

Fig. 17-11. Absorption spectra of cytochrome c in its oxidized (red line) and reduced (black line) forms. The characteristic absorption bands of the reduced form—a, ß, and γ—are indicated.

We now know that the cytochromes in the Respiratory Chain are arranged in the sequence b→с₁→с→аа₃ (Figs. 17-1 and 17-7). Cytochrome b, which exists in two forms, accepts electrons from ubiquinone and passes them to cytochrome c₁, which in turn transfers them to cytochrome c. Each of these cytochromes, while in its oxidized [Fe(III)] state, accepts a single electron and is converted to the reduced [Fe(II)] state. An iron-sulfur protein also participates in Electron transfer from ubiquinone to cytochrome c (Fig. 17-5). The final component in the chain of electron carriers is cytochrome aa₃, also known as cytochrome oxidase, because it transfers electrons directly to oxygen, thereby completing the transport process.

Cytochrome c is the most thoroughly studied of all cytochromes. It is a small protein (mol. wt. 12,500) containing an iron-porphyrin group covalently linked to a single polypeptide chain (Section 8.4). Its Amino Acid Sequence has been fully established (Fig. 6-14), and the detailed three-dimensional Structure of its molecules has been elucidated (Fig. 8-5). Cytochrome c is easily extracted from Cell/35.html">Mitochondria and has been obtained in crystalline form from numerous sources. As we noted earlier (Fig. 6-14), cytochrome c is one of the evolutionarily ancient proteins. This is evidenced by the remarkable conservation of its amino acid sequence across all eukaryotes, including microorganisms, plants, and animals.

Cytochrome aa₃ differs from other cytochromes. It contains two tightly bound molecules of heme A, which differs from hemoglobin protoheme by having a long hydrocarbon side chain attached to its porphyrin ring. In addition, it contains two crucial copper atoms. Upon accepting electrons from cytochrome c and thereby transitioning to the Fe(II) state, component a of the cytochrome transfers these electrons to cytochrome a₃. Reduced cytochrome a₃, in turn, passes the electrons to molecular oxygen (O₂). This process involves both iron-porphyrin groups and the two associated copper atoms, accompanied by a reversible change in their valence state [Cu(I)-Cu(II)]. This complex mechanism is a critical step in electron transport, as four electrons must be transferred almost simultaneously to O₂ to form two molecules of H₂O (the four H⁺ ions required for this reaction are drawn from the aqueous medium). Of all the carriers in the Electron Transport Chain, only cytochrome aa₃ is capable of reacting directly with oxygen.