Heme proteins reactions with oxygen

The synthesis and turnover of porphyrins that are precursors of heme are important hecanse of the central role of heme proteins, hemoglobin, and the cytochromes in reactions with oxygen and in electron transfer. Qnantitatively, hemoglobin synthesis is a major part of the nitrogen economy in hitmans. 

It has been shown that the activity of NO synthases is regulated by cofactors calcium binding protein calmodulin and tetrahydrobiopterin (H4B). Abu-Soud et al. [149] have studied the effect of H4B on the activity of neuronal nNOS I, using the isolated heme-containing oxygenase domain nNOSoxy. It was found that nNOSoxy rapidly formed an oxygenated complex in the reaction with dioxygen, which dissociated to produce superoxide (Reaction (6)) ... 

In the presence of ascorbate and oxygen, oxyMb and other heme proteins undergo a series of reactions that resemble the catalytic cycle of HO, albeit with less efficiency 278-281). Although the spectroscopic similarities of Mb and corresponding derivatives of HO are remarkable 264, 267, 272), the mechanism of the coupled oxidation reaction... 

This may transmit an electronic effect through either His F-8 or the heme ring to the nearby a, (32 interface and also affect the subunit interactions. The reaction of various heme proteins with oxygen is discussed further in Chapter 16. 

Reactions of Heme Proteins with Oxygen or Hydrogen Peroxide... 

Metalloenzymes of at least three different types catalyze the destruction of superoxide radicals that arise from reactions of oxygen with heme proteins, reduced flavoproteins, and other metalloenzymes. These superoxide dismutases (SODs) convert superoxide anion radicals 02 into H202 and 02 (Eq. 16-26). The H202 can then be destroyed by catalase (Eq. 16-8). 

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. 

The mechanism in hepatic cellular metabolism involves an electron transport system that functions for many drugs and chemical substances. These reactions include O-demethylation, N-demethyla-tion, hydroxylation, nitro reduction and other classical biotransformations. The electron transport system contains the heme protein, cytochrome P-450 that is reduced by NADPH via a flavoprotein, cytochrome P-450 reductase. For oxidative metabolic reactions, cytochrome P-450, in its reduced state (Fe 2), incorporates one atom of oxygen into the drug substrate and another into water. Many metabolic reductive reactions also utilize this system. In addition, there is a lipid component, phosphatidylcholine, which is associated with the electron transport and is an obligatory requirement for... 

Cytochrome c, a small heme protein (mol wt 12,400) is an important member of the mitochondrial respiratory chain. In this chain it assists in the transport of electrons from organic substrates to oxygen. In the course of this electron transport the iron atom of the cytochrome is alternately oxidized and reduced. Oxidation-reduction reactions are thus intimately related to the function of cytochrome c, and its electron transfer reactions have therefore been extensively studied. The reagents used to probe its redox activity range from hydrated electrons (I, 2, 3) and hydrogen atoms (4) to the complicated oxidase (5, 6, 7, 8) and reductase (9, 10, 11) systems. This chapter is concerned with the reactions of cytochrome c with transition metal complexes and metalloproteins and with the electron transfer mechanisms implicated by these studies. 

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