Oxidoreductase, models

The first test case was the ferrous high-spin state (Fe, S = 2) in the picket-fence porphyrin acetate complex [Fe(CH3COO)(TPpivP)] [13, 23], which is a model for the prosthetic group termed P460 of the multiheme enzyme hydroxyl-amine oxidoreductase from the bacterium Nitrosomonas europeae. Both the picket-fence porphyrin and the protein P460 exhibit an extraordinarily large quadrupole splitting, as observed by conventional Mossbauer studies [56]. 

Figure 2 Effect of enzyme immobilization on luminescent image spatial resolution evaluated using coupled enzymatic reactions on nylon net as a model system, (a) Immobilized 3a-hydroxysteroid dehydrogenase (b) immobilized 3a-hydroxysteroid dehydrogenase and FMN-NADH oxidoreductase (c) immobilized 3a-hydroxysteroid dehydrogenase, FMN-NADH oxidoreductase, and bacterial luciferase. (From Ref. 47. Copyright John Wiley Sons Ltd. Reproduced with permission.)...

This zinc metalloenzyme [EC 1.1.1.1 and EC 1.1.1.2] catalyzes the reversible oxidation of a broad spectrum of alcohol substrates and reduction of aldehyde substrates, usually with NAD+ as a coenzyme. The yeast and horse liver enzymes are probably the most extensively characterized oxidoreductases with respect to the reaction mechanism. Only one of two zinc ions is catalytically important, and the general mechanistic properties of the yeast and liver enzymes are similar, but not identical. Alcohol dehydrogenase can be regarded as a model enzyme system for the exploration of hydrogen kinetic isotope effects. 

Rates of hydroquinone glucuronidation in human liver microsomes showed a two- to three-fold variation between individual liver samples they were somewhat higher than in the rat, and lower than in the mouse liver (Seaton et al., 1995). A compartmental pharmacokinetic model was derived to describe the pharmacokinetics of hydroquinone in vivo in humans, rats and mice, incorporating hydroquinone glucuronidation rates sulfation of hydroquinone was not included in this model. NAD(P)H quinone acceptor oxidoreductases protect against reactive quinones by reducing them to the hydroquinone this enzyme seems to be absent in some individuals, which will lead to loss of such protection and make them more sensitive to hydroquinone toxicity (Ross, 1996). 

Brandt, U. (1997) Proton-translocation by membrane-bound NADH ubiquinone-oxidoreductase (complex I) through redoxgated ligand conduction. Biochim Biophys. Acta 1318, 79-91. Advanced discussion of models for electron movement through Complex I. 

We have already seen a number of models for the zinc(II) containing enzymes such as carbonic anhydrase in Section 11.3.2. Zinc is an essential component in biochemistry, and forms part of the active site of more then 100 enzymes, of which hydrolases (such as alkaline phosphatase and carboxypeptidase A), transferases (e.g. DNA and RNA polymerase), oxidoreductases (e.g. alcohol dehydrogenase and superoxide dismutase) and lysases (carbonic anhydrase) are the most common. In addition, the non-enzyme zinc finger proteins have an important regulatory function. In many of these systems, the non-redox-active Zn2+ ion is present as a Fewis acidic centre at which substrates are coordinated, polarised and hence activated. Other roles of zinc include acting as a template and playing a structural or regulatory role. 

Figure 12.5 Proposed mechanism for the cyclic oxidation of primary alcohols by molecular oxygen catalyzed by a photodriven model of native oxidoreductase - the antimony(V) oxo...

Much of the chemistry described in this article resulted from the search for complexes modeling structural and functional features of metal-sulfur oxidoreductases such as hydrogenases, CO dehydrogenases, and, in particular, nitro-genases. Complexes were sought that exhibited sulfur dominated coordination... 

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