Oxidative enzymes oxidases

Oxidative Reactions. The majority of pesticides, or pesticide products, are susceptible to some form of attack by oxidative enzymes. For more persistent pesticides, oxidation is frequently the primary mode of metaboHsm, although there are important exceptions, eg, DDT. For less persistent pesticides, oxidation may play a relatively minor role, or be the first reaction ia a metaboHc pathway. Oxidation generally results ia degradation of the parent molecule. However, attack by certain oxidative enzymes (phenol oxidases) can result ia the condensation or polymerization of the parent molecules this phenomenon is referred to as oxidative coupling (16). Examples of some important oxidative reactions are ether cleavage, alkyl-hydroxylation, aryl-hydroxylation, AJ-dealkylation, and sulfoxidation. 

Hurst (19) discusses the similarity in action of the pyrethrins and of DDT as indicated by a dispersant action on the lipids of insect cuticle and internal tissue. He has developed an elaborate theory of contact insecticidal action but provides no experimental data. Hurst believes that the susceptibility to insecticides depends partially on the cuticular permeability, but more fundamentally on the effects on internal tissue receptors which control oxidative metabolism or oxidative enzyme systems. The access of pyrethrins to insects, for example, is facilitated by adsorption and storage in the lipophilic layers of the epicuticle. The epicuticle is to be regarded as a lipoprotein mosaic consisting of alternating patches of lipid and protein receptors which are sites of oxidase activity. Such a condition exists in both the hydrophilic type of cuticle found in larvae of Calliphora and Phormia and in the waxy cuticle of Tenebrio larvae. Hurst explains pyrethrinization as a preliminary narcosis or knockdown phase in which oxidase action is blocked by adsorption of the insecticide on the lipoprotein tissue components, followed by death when further dispersant action of the insecticide results in an irreversible increase in the phenoloxidase activity as a result of the displacement of protective lipids. This increase in phenoloxidase activity is accompanied by the accumulation of toxic quinoid metabolites in the blood and tissues—for example, O-quinones which would block substrate access to normal enzyme systems. The varying degrees of susceptibility shown by different insect species to an insecticide may be explainable not only in terms of differences in cuticle make-up but also as internal factors associated with the stability of oxidase systems. 

Ketoreductases catalyze the reversible reduction of ketones and oxidation of alcohols using cofactor NADH/NADPH as the reductant or NAD + /NADP+ as oxidant. Alcohol oxidases catalyze the oxidation of alcohols with dioxygen as the oxidant. Both categories of enzymes belong to the oxidoreductase family. In this chapter, the recent advances in the synthetic application of these two categories of enzymes are described. 

As mentioned before, the main problem for the application of such oxidizing enzymes in organic synthesis is the availability of an effective reactivation method for the prosthetic groups or the freely dissociated cofactors. Especially, the long-term stability of the whole system is the limiting factor [25]. All oxidases mentioned previously can be reactivated by an aerobic... 

Another oxidizing enzyme with very interesting synthetic potential is galactose oxidase [14]. This copper protein oxidizes primary hydroxy functions in polyols enantioselectively to the corresponding aldehydes. Thus, sugar alcohols may be transformed into the interesting non-natural L-configurated... 

Compound I is a two-electron oxidized enzyme intermediate containing a oxyferryl iron and a porphyrin cation radical while compound II is an one-electron oxidized intermediate (13), With lignin pa oxidase, as with other peroxidases, the substrate oxidation products are fir radicals which undergo nonenzymatic disproportionation reactions to give rise to the final products. 

The amino groups are replaced with oxygen. Although here a biochemical reaction, the same can be achieved under acid-catalysed hydrolytic conditions, and resembles the nucleophilic substitution on pyrimidines (see Section 11.6.1). The first-formed hydroxy derivative would then tautomerize to the carbonyl structure. In the case of guanine, the product is xanthine, whereas adenine leads to hypoxanthine. The latter compound is also converted into xanthine by an oxidizing enzyme, xanthine oxidase. This enzyme also oxidizes xanthine at C-8, giving uric acid. 

A flavoprotein oxidase, which is also a methanol oxidizing enzyme, was inhibited by cyclopropanol 4 through the formation of a N-5 flavin adduct with a ring opened cyclopropyloxy radical [10]. 

Chemoenzymatic processes involving oxidizing enzymes have been reported particularly for specific chemical syntheses. For example, industrially important amino acids can be deracemized by exploiting the enantioselectivity of amino acid oxidases a commercial process has recently been developed in which efficient... 

Bioelectrocatalysis involves the coupling of redox enzymes with electrochemical reactions [44]. Thus, oxidizing enzymes can be incorporated into redox systems applied in bioreactors, biosensors and biofuel cells. While biosensors and enzyme electrodes are not synthetic systems, they are, essentially, biocatalytic in nature (Scheme 3.5) and are therefore worthy of mention here. Oxidases are frequently used as the biological agent in biosensors, in combinations designed to detect specific target molecules. Enzyme electrodes are possibly one of the more common applications of oxidase biocatalysts. Enzymes such as glucose oxidase or cholesterol oxidase can be combined with a peroxidase such as horseradish peroxidase. 

Lignin peroxidase activity, (i.e., peroxide-dependent oxidation of veratryl alcohol at pH 3) was not detected over the 30 days tested, while laccase appeared at day 7. Culture medium from day 7 onwards could also oxidize veratryl alcohol to aldehyde with concomitant conversion of oxygen to hydrogen peroxide. This activity, which was optimal at pH 5.0, was named veratryl alcohol oxidase (VAO). The extracellular oxidative enzyme activities (laccase and veratryl alcohol oxidase) could be separated by ion-exchange chromatography (Figure 2). Further chromatography of the coincident laccase and veratryl alcohol oxidase (peak 2), as described elsewhere (25) resulted in the separation of two veratryl alcohol oxidases from the laccase. 

The products of oxidation are easily visualized shortly after ozone treatments but no claim should be made that phenolics or the oxidative enzymes, polyphenol oxidase, phenolase or peroxidase... 

Mixed Function Oxidases Oxidizing enzymes which are involved in die metabolism of many foreign compounds giving products of different toxicity front the parent compound. 

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