Oxidative enzymes oxygenases

Other mono-oxygenases are not cytochrome P450 dependent, such as flavoproteins located in the endoplasmic reticulum that are involved in the oxidation of tertiary amines to N-oxides and of various sulfur compounds. Yet other oxidative enzymes, including alcohol and aldehyde dehydrogenases and monoamine oxidases, are located in the mitochondria or cytosol. 

Class III peroxidases have been the subject of numerous studies [10] and applications [11], since their extraordinary catalytic properties make them a valuable catalytic tool in the plant cell chemical factory, and in organic synthesis. In fact, class III peroxidases, together with other oxidative enzymes, such as cytochrome P450s and oxygenases [12], appear to be the main driving force in the evolution of plant metabolic pathways because individual enzymes can typically accept multiple substrates and form several products. This metabolic plasticity of class III peroxidases, paradoxically, has frequently led to misunderstanding of its vital function in the plant cell biochemical factory. 

In another subset of reactions, O2 donates either one or both of its oxygen atoms to an acceptor (for example, see xanthine oxidase. Fig. 8.19). When this occurs, O2 becomes reduced, and an electron donor is oxidized. Enzymes participating in reactions with O2 are called hydroxylases and oxidases when one oxygen atom is incorporated into a substrate and the other oxygen atom into water, or both atoms are incorporated into water. They are called oxygenases when both atoms of oxygen are incorporated into the acceptor. Most hydroxylases and oxidases require metal ions, such as Fe, for electron transfer. 

Oxidations. Most oxidative processes take place in liver microsomes and are catalysed by mono-oxygenase enzymes known as mixed-function oxidases. These processes require reduced nicotinamide-adenine dinucleotide phosphate, molecular oxygen and a complex of enzymes in the endoplas-matic reticulum. The terminal oxidizing enzyme is cytochrome P450, a hemoprotein. The notation P450 refers to the ability of the reduced (ferrous) form of the hemoprotein to react with carbon monoxide, yielding a complex with absorption peak at 450 nm. For each molecule... 

Oxidations - Enzymes which functionalize inactivated carbon are often difficult to obtain and handle. Many examples exist of oxidations using microbial fermentations, e.g. for steroids, and recently in olefin oxidation.Such preparative transformations have not been achieved with purified enzymes and are unlikely to be amenable to large-scale in vitro approaches because of instability and complexity of the enzyme systems. Klibanov and coworkers, however, have developed systems with horseradish peroxidase and xanthine oxidase for oxidation of aromatic alcohols and amines, for use in syntheses and waste water treatment. Hydroxyphenyl compounds can be oxidized to dihydroxy derivatives. L-DOPA has been made from L-tyrosine in this manner.Cyclohexanone was oxidized to t-caprolactone with a bacterial oxygenase. 

Nothing is known about the identity of the iron species responsible for dehydrogenation of the substrate. Iron-oxo species such as FeIV=0 or Fem-OOH are postulated as the oxidants in most heme or non-heme iron oxygenases. It has to be considered that any mechanistic model proposed must account not only for the observed stereochemistry but also for the lack of hydroxylation activity and its inability to convert the olefinic substrate. Furthermore, no HppE sequence homo-logue is to be found in protein databases. Further studies should shed more light on the mechanism with which this unique enzyme operates. 

These include the mitochondrial respiratory chain, key enzymes in fatty acid and amino acid oxidation, and the citric acid cycle. Reoxidation of the reduced flavin in oxygenases and mixed-function oxidases proceeds by way of formation of the flavin radical and flavin hydroperoxide, with the intermediate generation of superoxide and perhydroxyl radicals and hydrogen peroxide. Because of this, flavin oxidases make a significant contribution to the total oxidant stress of the body. 

These enzymes catalyze a variety of oxidative reactions in natural product biosynthesis with two C—Hhydroxylation examples shown in Figure 13.24 [72,73]. It should be noted thatC—H activation by nonheme iron oxygenases, such as aromatic dioxygenases, is an important pathway in degradation of aromatics into m-dibydrodiols, which are important chiral building blocks for chemical synthesis [74,75]. 

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