Heme cytochrome P450

Cytochrome P450 monooxygenases are characterized through the presence of the heme (protoporphyrin IX) prosthetic group (Scheme 10.1) that is coordinated to the enzyme through a conserved cysteine ligand. They have obtained their name from the signature absorption band with a maximum near 450 nm in the difference spectrum when incubated with CO. The absorption arises from the Soret Jilt transition of the ferrous protoporphyrin IX-CO complex. 

Some of the major enzyme groups that facilitate this transformation are heme-containing MOs of the cytochrome P450 type [111], alkane hydroxylases, xylene monooxygenases, styrene monooxygenases [105], and haloperoxidases [112],... 

Many drugs when administered to humans can result in a marked increase in ALASl. Most of these drugs are metabolized by a system in the liver that utilizes a specific hemoprotein, cytochrome P450 (see Chapter 53). During their metabolism, the utilization of heme by cytochrome P450 is greatly increased, which in turn diminishes the intracellular heme concentration. This latter event effects a derepression of ALASl with a corresponding increased rate of heme synthesis to meet the needs of the cells. 

It is estimated that 1 g of hemoglobin yields 35 mg of bihmbin. The daily bihmbin formation in human adults is approximately 250-350 mg, deriving mainly from hemoglobin but also from ineffective erythro-poiesis and from various other heme proteins such as cytochrome P450. 

Isoforms of Cytochrome P450 Make Up a Superfamily of Heme-Containing Enzymes... 

Loew GH, Harris DL. 2000. Role of the heme active site and protein environment in structure, spectra and function of the cytochrome P450s. Chem Rev 100 407. 

Gosh et al. reported LDA(SVWN) studies of oxo(porphyrinato)iron(IV) complexes.83 These compounds have been detected in various peroxidases and are believed to be involved in the reaction mechanisms of other heme enzymes, such as cytochromes P450. Very Good Fe-0 distance and values of unsealed stretching frequencies, which were in excellent agreement with CASSCF results, published elsewhere, were obtained. 

Figure 8.1 Schematic of a typical cytochrome P450 protein showing the approximate locations for the heme binding domain, the proline-rich region and the I helix.

In the field of enzyme catalysis, heme-proteins such as cytochrome P450, for example, exhibit both types of 0-0 bond cleavages in organic hydroperoxides and peroxy acids (178). Heterolytic cleavage of HOOH/ROOH yields H20 or the corresponding alcohol, ROH and a ferryl-oxo intermediate (Scheme 4). Homolytic 0-0 bond cleavage results in the formation of a hydroxyl (HO ) or an alkoxyl (RO ) radical and an iron-bound hydroxyl radical. 

---