Cytochrome P450 electron transport system

Figure 3 Cytochrome P450 electron transport system. S, Substrate.

Protein-mediated electron transfer is a device used in a diverse array of biological transformadons. Well-known electron transfer processes include the mitochondrial electron transport system, photosynthesis (Chapter 13), and nitrogen flxadon (Chapter 15). Less well known biochemical reactions in which electron transfer plays a crucial role include nitric oxide synthesis and the cytochrome P450 electron transport systems. Each of these mechanisms is briefly oudined. 

Cytochrome P450 electron transport systems are an important feature of biotransformation in animal bodies. Biotransformation is a series of enzyme-catalyzed processes in which potentially toxic and usually hydrophobic substances are converted into less toxic water-soluble derivatives that can then be more easily excreted. Substrates for biotransformation include endogenous substances, such as cholesterol, and foreign molecules, called xenobiotics, such as drugs and nonnutritive components of food (e.g., glycosides and numerous fatty acid and amino acid derivatives). 

Examples of endogenous biotransformation reactions catalyzed by cytochrome P450 electron transport systems include the synthesis of steroid hormones from cholesterol (Chapter 12) and the conversion of vitamin D3 to its biologically active form 1,25-dihydroxyvitamin D3. 

As mentioned (see p. 320), ROS are generated during several other cellular activities besides the reduction of Oz to form H20. These include the biotransformation of xenobiotics and the respiratory burst (Figure 10.20) in white blood cells. In addition, electrons often leak from the electron transport pathways in the endoplasmic reticulum (e.g., the cytochrome P450 electron transport system) to form superoxide by combining with Oz. 

Scheme 10.3 Electron-transport systems associated with cytochrome P450 monooxygenases. Arrows indicate electron transfer.

Heme oxygenase, which catalyzes the conversion of free heme groups to biliverdin and CO, functions as part of a microsomal electron transport system similar to that of cytochrome 1 450-(FP = NADPH-cytochrome P450 reductase.) Heme oxygenase requires 3 02 and 5 NADPH. Biliverdin reductase can use NADPH or NADH as a reductant. 

Green AJ, Munro AW, Rivers SL, Reid GA, Chapman SK (2001) Reconstituting the electron transport system in cytochrome P450. Biol Biochem Soc Trans 29 A34-A34... 

The smooth endoplasmic reticulum contains enzymes involved in reactions of oxidation and hydroxylation of many types of molecules (alcohols, barbitiuates, antibiotics, steroid hormone synthesis and metabolism, etc.). These enzymes use cytochrome P450 and b as electron transport system and can also generate 02 and/or H2O2. 

The existence of mitochondrial cytochrome P450 in adrenal cortex was reported originally by Harding et al (1964) and confirmed by subsequent studies. Adrenal cortical mitochondria catalyze a number of NADPH- and molecular-oxygen-dependent hydroxylation reactions that contribute to the biosynthesis of corticosteroids. The enzyme system for 11 jS-hydroxyla-tion has been isolated, and a successful reconstitution of its activity has been achieved by the interaction of three proteins, namely an NADPH-dependent flavoprotein (adrenodoxin reductase), an iron-sulfur protein (adrenodoxin), and the heme protein (cytochrome P450) that serves as the terminal oxidase for the electron transport system from NADPH to oxygen (Wang and... 

Microsomal reduction of chromium(VI) can also result in the formation of chromium(V), which involves a one-electron transfer from the microsomal electron-transport cytochrome P450 system in rats. The chromium(V) complexes are characterized as labile and reactive. These chromium(V) intermediates persist for 1 hour in vitro, making them likely to interact with deoxyribonucleic acid (DNA), which may eventually lead to cancer (Jennette 1982). Because chromium(V) complexes are labile and reactive, detection of chromium(V) after in vivo exposure to chromium(VI) was difficult in the past. More recently, Liu et al. (1994) have demonstrated that chromium(V) is formed in vivo by using low-frequency electron paramagnetic resonance (EPR) spectroscopy on whole mice. In mice injected with sodium dichromate(VI) intravenously into the tail vein, maximum levels of chromium(V) were detected within 10 minutes and declined slowly with a life time of about 37 minutes. The time to reach peak in vivo levels of chromium(V) decreased in a linear manner as the administered dose levels of sodium... 

Hannemann F, Bichet A, Ewen KM, Bernhardt R. Cytochrome P450 systems—biological variations of electron transport chains. Biochim. Biophys. Acta 2007 1770 330-344. 

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