Haem group

Figure 2.2 (a) A detailed picture of the haem group and its binding site within myoglobin or... 

There are two types of electron transport those involving flavoproteins and iron-sulfur proteins, and those requiring only flavoproteins. The X-ray crystal structure of the soluble cytochrome P450 from Pseudomonas putida grown on camphor (P-450-CAM) has been determined (Poulos et ah, 1985), as have several others. The haem group is deeply embedded in the hydrophobic interior of the protein, and the identity of the proximal haem iron ligand, based on earlier spectroscopic studies (Mason et ah, 1965) is confirmed as a specific cysteine residue. 

Figure 2.6 Chemical structures (a) and axial ligands (b) to the haem groups in cytochromes a, b and c. From Voet and Voet, 1995. Reproduced by permission of John Wiley Sons, Inc.

Figure 4.2 Hypothetical plasma membrane (PM)-associated structure of FR02. Four histidine residues (white spots) predicted to coordinate two intramembraneous haem groups (white bars) are indicated, as are the tetrapeptide binding sites for FAD and N AD(P)H. The sites of mutations in the FRO gene are indicated (frdl-l,frdl-3) i, inside cell o, outside cell. Reprinted with permission from Nature (Robinson et al., 1999). Copyright (1999) Macmillan Magazines Limited.

IX is accompanied by its transport back into the mitochondria whence it came, to undergo oxidation of its methylene groups to protoporphyrin IX and insertion of iron to yield the end product, haem. The two major sites of haem biosynthesis are erythroid cells, which synthesize around 85 % of the body s haem groups, and the liver, which synthesizes most of the remainder. A major function of haem in liver is as the prosthetic group of cytochrome P450, the importance of which in detoxification has been discussed in Chapter 2. The liver cell must synthesize cytochrome P450 throughout its lifetime in quantities that vary with conditions. In contrast, the... 

Figure 9.5. Attachment of the haem group to the globin chain via a coordinated histidine group.

Figure 13.6 The haem group and its environment in the deoxy form of the human haemoglobin a-chain. Only selected side chains are shown, and the haem 4 propionate is omitted for clarity. (From Gelin and Karplus, 1977. Copyright (1993) National Academy of Sciences, USA.)...

Ortiz de Montellano, P.R. and Mathews, J.M. (1981) Autocatalytic alkylation of the cytochrome P-450 prosthetic haem group by 1-aminobenzotriazole. Isolation of an NN-bridged benzyne-protoporphyrin IX adduct. Biochemical Journal, 195 (3), 761-764. 

The principles of ESR spectroscopy are very similar to NMR spectroscopy but the technique gives information about electron delocalizations rather than molecular structure and it enables the study of electron transfer reactions and the formation of paramagnetic intermediates in such reactions. In some situations, information regarding molecular structure can be obtained when suitable prosthetic groups are part of a molecule, e.g. FMN (flavin mononucleotide) in certain enzymes or the haem group in haemoglobin. Sometimes it is possible to attach suitable groups to molecules to enable their reactions to be monitored by ESR techniques. Such spin labels as they are called, are usually nitroxide radicals of the type... 

Many enzymes require additional substances in order to function effectively. Conjugated enzymes require a prosthetic group before they are catalytically active, such groups being covalently or ionically linked to the protein molecule and remaining unaltered at the end of the reaction. Catalase (EC 1.11.1.6), for instance, contains a haem group while ascorbate oxidase (EC 1.10.3.3) contains a copper atom. 

Acting on a haem group of donors 1.14.16 of oxygen With reduced pteridine as one donor, and... 

In natural systems dimerization reactions are prevented by the location of the haeme group in a sterically protected protein pocket, which prevents another haeme group approaching and attacking the original haeme. Analogously, protonation reactions are limited by the fact that the haeme group lies in a hydrophobic pocket. 

Figure 9 shows schematically a few Fe(II) complexes, which model the haeme group and contain bulky groups to prevent dimerization.13... 

Mitochondrial function. NO is able to react with transition metals such as iron, including those contained within haem groups. Even at low NO concentrations there is competition between oxygen and NO for reversible binding to cytochrome c oxidase. If mitochondrial 02 is low respiration slows, which may confer anti-apoptotic benefit to the cell. As NO concentration rises and peroxynitrite is formed, electron transport is irreversibly inhibited, there is increased production of superoxide and other reactive oxygen species and apoptosis occurs. 

Circulating RBCs lack the enzymes to produce either haem groups or globin chains so the synthesis of haemoglobin is a defining feature of early RBC maturation. Globin chain production is like the formation of any other protein, but a and 3 chain synthesis is closely linked with haem synthesis. 

Fully oxygenated haemoglobin releases one atom of O2 and the haem group-iron remains in the reduced state. 

IV electron transfer from oxygen to haem group of P-450 (Fe2+—> Fe3+)... 

Two examples will be used to illustrate phase I and phase II reactions paracetamol and the catabolism of haem groups. 

Free haem groups are ferroporphyrins (cyclic tetrapyrroles). The first reaction of haem catabolism is the release of iron this is followed by the opening of the ring to produce a linear tetrapyrrole called biliverdin. A molecule of carbon monoxide is released as the ring opens. Biliverdin is converted to bilirubin by reduction. These initial reactions may occur in the liver or in other tissues of the reticuloendothelial system, notably the spleen. 

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