Activation of Molecular Oxygen by Cytochrome

MakrisTM, Denisov I. SchlichTing I, et al. Activation of molecular oxygen by cytochrome P450. In Ortiz de Montellano PR. ed. Cytochrome P450 structure mechanism and biochemistry, 3rd Ed. New York. Plenum Press, 2005, pp149-182. 

The biochemical importance of flavin coenzymes ap-pears to be their versatility in mediating a variety of redox processes, including electron transfer and the activation of molecular oxygen for oxygenation reactions. An especially important manifestation of their redox versatility is their ability to serve as the switch point from the two-electron processes, which predominate in cytosolic carbon metabo-lism, to the one-electron transfer processes, which predomi-nate in membrane-associated terminal electron-transfer pathways. In mammalian cells, for example, the end products of the aerobic metabolism of glucose are C02 and NADH (see chapter 13). The terminal electron-transfer pathway is a membrane-bound system of cytochromes, nonheme iron proteins, and copper-heme proteins—all one-electron acceptors that transfer electrons ultimately to 02 to produce H20 and NAD+ with the concomitant production of ATP from ADP and P . The interaction of NADH with this pathway is mediated by NADH dehydrogenase, a flavoprotein that couples the two-electron oxidation of NADH with the one-electron reductive processes of the membrane. 

It has been hypothesized that activated BLM is a high-valent iron-0X0 complex generated by a reductive activation of molecular oxygen reminiscent to that observed in cytochrome P-450 monooxygenases... 

One motivation for the characterization of the above compounds has been to more fully understand the involvement of such higher valent manganese porphyrin complexes in model systems which imitate the catalytic activity of monooxygenase cytochrome P-450 and related enzymes. The catalytic cycle of cytochrome P-450 appears to involve the binding and reduction of molecular oxygen at a haem centre followed by the ultimate formation of a reactive iron oxo complex which is responsible for oxidation of the substrate. For example, cytochrome P-450 is able to catalyse alkane hydroxylation with great selectivity. 

GALDH shows a high enantio-preference for L-galactono-1,4 -lactone (13). Reoxidation of the two-electron reduced enzyme by cytochrome c occurs in two single-electron steps and involves the intermediate formation of the red anionic flavin semiquinone (Fig. lb). Related aldonolactone oxidoreductases act as true oxidases, which suggests that they provide a better access of molecular oxygen to the active site. 

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