Biomedical Engineering Reference
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revelation of several important structural and mechanistic features of this unique
catalytic center.
1. The iron atoms in FeMoco have non-saturated coordination spheres to give the
opportunity for dinitrogen molecules to interact with two or more iron atoms.
2. The dinitrogen coordination has to be suitable for the overlap of both filled binding
and empty antibonding dinitrogen orbitals with d-orbitals of iron atoms.
3. Three-four electrons and three-four protons should be transferred to the dinitrogen to
activate the molecule for subsequent reduction of the hydrazine derivative to ammonia.
4. The FeMoco structure has be flexible enough to provide a free space for dinitrogen to
come into in the cofactor cavity, transformating and then coming out from the cofactor.
All these conclusions agree in principle with above-mentioned earlier considerations
about the mechanism of nitrogen reduction under mild conditions. The dinitrogen
reduction occurs in the polynuclear FeMo-cofactor. Available experimental and
theoretical data allow us to conclude that the enzyme nitrogenase can overcome the high
chemical inertness of dinitogen using the energetically favorable four-electron
mechanism in which a hydrazine derivative appears to be the first intermediate product.
The accumulation of reducing power, due to consecutive four one electron and one
proton transfers, precedes the dinitrogen reduction.
3.2.
Cytochrome P-450
3.2.1. OVERVIEW
Powerful enzyme hydroxylation systems of organic substrates, i.e. steroids,
hydrocarbons, organic acids, alcohols and amines, are operatives in animal and plant
tissues and bacteria (Coon et al., 1981; Guengerich and Mcdonald (1984); Weiner, 1986;
Sono et al., 1996; Oriz de Montellano, 1995; Sono et al., 1996; Newcomb et al., 2000;
Ogliaro et al., 2000, 2001; and references therein). These enzymes catalyze oxidation
processes according to the following general scheme:
where RH is the substrate and DH is the reducing agent (NADH or NADH with the use
of the appropriate reductase). The action of these systems on compounds having
unsaturated bonds may result in their epoxidation or demethylation with methylamines.
They are involved in a number of vital processes including the biosynthesis of steroids,
degradation of xenobiotics, drug metabolism, and carcinogenesis.
The hydroxylation reaction is directly effected by an enzyme-hemoprotein,
monooxigenase, cytochrome P450 containing protocheme IX. The reduction of the
enzyme involves flavin reductases and electron carriers, such as adrenodoxin,
rubredoxin, and cytochrome Dioxygen, being a weak one-electron oxidant, is
activated after the reduction in the enzyme heme coordination sphere. The various forms
of cytochrome P450 from liver microsomes and from Pseudomonas putida have a
molecular mass of about 49000. One of the subunits of the enzyme from mitochondria of
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