Redox enzymes flavoenzymes

It is well known that the flavin adenine dinucleotide redox centers of many oxidases are electrically inaccessible due to the insulating effect of the surrounding protein thus, direct electron transfer from the reduced enzyme to a conventional electrode is negligible. In the present work, a variety of polymeric materials have been developed which can facilitate a flow of electrons from the flavin redox centers of oxidases to an electrode. Highly flexible siloxane and ethylene oxide polymers containing covalently attached redox moieties, such as ferrocene, are shown to be capable of rapidly re-oxidizing the reduced flavoenzyme. 

FerredoxinrNADP oxidoreductase (FNOR, EC 1.18.1.2) is a flavoenzyme that catalyzes electron transfer between the redox protein, ferredoxin, and the pyridine nucleotide coenzymes, NADP(H) and/or NAD(H). Enzymes of this type have been characterized from many organisms, including from both the bacterial and eukaryotic domains. " However, only one such enzyme has been purified from... 

Further examples of recycling enzyme pairs include copper enzymes such as laccase and tyrosinase which oxidizes a wide range of substances including catecholamines, phenols, and redox dyes by dissolved oxygen in combination with flavoenzymes, haem-, and pyrroloquino-line quinone containing (NADTf independent) dehydrogenases. 

In an aqueous solution, free flavin species exist in a pH-dependent equilibrium, shown in Figure 6.2, as proposed by Heelis (1982). Among the nine forms presented (derived from different redox and protonation states), at least six are physiologically relevant according to their p.Ka values. At neutral pH, only approximately 5% of flavins are found in an equimolar mixture of completely oxidized and reduced flavins, with most being found as the semiquinone in neutral or anionic forms (pifa 8.5). Upon binding to a protein, such equilibrium changes drastically. In some enzymes, flavins may be found almost completely in the semiquinone forms, while in other enzymes these forms are not observed. Moreover, the of flavoenzymes may be shifted up or down if the protein can stabilize the neutral radical species or the semiquinone anion, respectively (Miura 2001). 

Riboflavin, commonly known as vitamin B2, is metabolized inside cells to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), two very important enzyme cofactors. These molecules possess rather unique and versatile chemical properties, which confer on them the ability to be among the most important redox cofactors found in a broad range of enzymes. In this chapter we provide a brief description of riboflavin metabolism and chemistry, overview the different flavoenzymes engaged in fatty acid p-oxidation and their respective roles. We also highlight recent studies shedding light on the cellular processes and biological effects of riboflavin supplementation in the context of metabolic disease. 

It is, however, better known that flavoenzymes (i.e., enzymes utilizing the flavin adenine dinucleotide [FAD FADH2] redox system) mediate the introduction of a,P carbon-carbon double bonds into carboxylic acids and into acetyl Coenzyme A (acetyl CoA) thioesters of long-, medium-, and short-chain fatty acids. In carboxylic acids, such as those of the tricarboxylic acid (citric acid, TCA, or Krebs) cycle (Chapter 11) the oxidation is affected by the enzyme sucdnate dehydrogenase (fumerate reductase— EC 1.3.99.1), which utilizes the cofactor flavin adenine dinucleotide (FAD) The latter is reduced to FADH2 and an ( )-double bond is introduced. The process shown in Scheme 9.105, for the conversion of succinate (1,4-butanedioic acid) to fumerate [(E)-l,4-butenedioic acid], is a fragment of the tricarboxylic acid (citric acid, TCA, or Krebs) cycle (Chapter 11), which is the pathway commonly utilized for oxidative degradation of acetate to carbon dioxide. 

Flavins are a group of natural enzyme cofactors with interesting redox and photochemical properties that can participate in a wide set of reactions [12]. The most common flavin cofactors are flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD). Enzymes harboring one of these cofactors are called flavoenzymes. A large number of flavoenzymes have been extensively studied for their structural and mechanistic properties, and they are gaining momentum in industrial biocata-lytic applications [13,14], Flavoenzymes have evolved to become powerful oxidative biocatalysts they can catalyze not only simple alcohol oxidations but they were also foimd to be efficient in catalyzing, for example, oxidative C—C bond formation and enantioselective sulfoxidations. 

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