CYTOCHROME P450 : A MONOOXYGENASE 361
in the cytochrome bc 1 complex, also known as ubiquinol : ferricytochrome c
oxidoreductase (EC 1.10.99.1). One can search the http://www.expasy.org/
enzyme/ site to fi nd more information about any enzyme by entering its name.
The EC terminology is established by the Nomenclature Committee of the
International Union of Biochemistry and Molecular Biology (NC - IUBMB)
at http://www.chem.qmul.ac.uk/iubmb/nomenclature/. Cytochrome b binds a
high (b H ; b 560 or b 562 ) and a low (b L ; b 566 or b 565 ) potential heme group. These
two cytochromes will be discussed in detail in Sections 7.5 and 7.6. Cytochrome
P450, discussed in Section 7.4 , also contains a cytochrome b.
Cytochrome P450 enzymes are monooxygenases that insert one atom of a
dioxygen molecule into a substrate. A wide variety of organic molecules are
oxygenated by cytochrome P450. The other oxygen atom of the dioxygen
molecule is converted to water during the P450 catalytic cycle (Section 7.4).
Cytochrome P450 has its own dedicated website maintained by D. R. Nelson
at http://drnelson.utmem.edu/CytochromeP450.html.
7.4 Cytochrome P450: A Monooxygenase,
7.4.1 Introduction,
The cytochrome P450 metalloenzyme is one of a large group of iron -
containing oxygenases that utilize atmospheric dioxygen to functionalize mol-
ecules using cofactors such as fl avins or NAD(P)H as well as non - heme iron
or copper and other metalloporphyrin complexes. Cytochromes P450 are
known to protect the body from foreign chemicals by oxidizing toxic com-
pounds to metabolically manageable hydrophilic materials. As such, they can
be thought of as physiological permanganate ions ( MnO 4 −). However, P450s
can produce toxic or carcinogenic compounds in vivo. The cytochrome P450
metalloenzyme contains an iron – heme cofactor similar to that found in hemo-
globin or myoglobin — that is, it is a metalloporphyrin. The porphyrin itself,
called protoporphyrin IX, or heme b (see Figure 7.1 ), contributes four N - donor
ligands to the iron ion ’ s coordination sphere in a planar (or nearly planar)
arrangement. The metalloenzyme ’ s name resulted from early experimentation:
Cytochrome means “ cellular pigment ” or “ P ” and 450 refers the wavelength
of the absorption maximum found for its ferrous - CO derivative.^32 Cytochrome
P450s are ubiquitous in biological systems, and many of them are membrane -
bound. The basic reaction catalyzed is
RH O++ + ⎯ 2222 H+−e NAD P H⎯⎯⎯()→ROH H O+ (7.7)
While the uncatalyzed reaction requires extremely high temperatures and
proceeds nonspecifi cally, the enzymatic reaction proceeds regiospecifi cally
and stereospecifi cally under physiological conditions of temperature and pres-
sure. The P450 enzyme utilizes its iron – porphyrin centers as metal - containing