Heme groups monooxygenase

The enzyme is a cytochrome P-450 monooxygenase, which is reflected in its properties. It is membrane-bound, is dependent on NADPH and molecular oxygen, and displays a light-reversible inhibition by carbon monoxide. Cytochrome P-450 enzymes are dependent on a membrane-bound reductase (NADPH cytochrome P-450 reductase, EC 1.6.2.4), a flavopro-tein that is involved in the electron transfer from NADPH to the cytochrome P-450 heme group. 

The ferroxidase center, important for rapid oxidation of Fe to Fe, was discovered relatively recently in the history of research into the metal sites in ferritins. Ferroxidase activity within H subunits appears to occur at a dinuclear site situated within a four-helix bundle and resembling the dinuclear centers found in ribonucleotide reductase, methane monooxygenase, fatty acid desaturases, and ruberythrin (Chapter 8.11). In bacterioferritins, for which protein crystal structures have been reported for ferritin from Escherichia col and Rhodobacter capsulatus the overall motif of a shell of 24 subunits with relative masses of about 18,500 Da is preserved but there are also 12 protoporphyrin IX heme groups present with unknown function which might have a role in connecting the dimer units and are buried within the shell between identical subunits related by twofold symmetry. In these bacterioferritins the subunits are all identical and contain both ftrroxidase and nucleation sites. 

Scheme 5.2 Catalytic cycle of P450 monooxygenases. In P450, the heme group is bound to the protein backbone via cysteine (Cys-S-). RH indicates the substrate. Numbering indicates different heme iron species (for details refer to main text).

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],... 

The monooxygenase group of enzymes includes the non-P450 hydroxylases which catalyze the insertion of a hydroxyl group to replace a hydrogen atom at a saturated carbon [6-8] and the non-heme-dependent oxygenases such as the flavin-molybdenum-cobalt-dependent xanthine oxidase and aldehyde oxidase... 

Cytochromes P450 are monooxygenases whose cosubstrates, often NADH or NADPH, deliver electrons to the active center heme via a separate flavoprotein and often via an iron-sulfur protein as well 476a b A typical reaction (Eq. 18-55) is the 11 (3-hydroxylation of a steroid, an essential step in the biosynthesis of steroid hormones (Fig. 22-11). The hydroxyl group is introduced without inversion of configuration. The same enzyme converts unsaturated derivatives to epoxides (Eq. 18-56), while other cytochromes P450... 

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