Electron transfer flavoenzyme catalyzed

Pyridine nucleotide-dependent flavoenzyme catalyzed reactions are known for the external monooxygenase and the disulfide oxidoreductases However, no evidence for the direct participation of the flavin semiquinone as an intermediate in catalysis has been found in these systems. In contrast, flavin semiquinones are necessary intermediates in those pyridine nucleotide-dependent enzymes in which electron transfer from the flavin involves an obligate 1-electron acceptor such as a heme or an iron-sulfur center. Examples of such enzymes include NADPH-cytochrome P4S0 reductase, NADH-cytochrome bs reductase, ferredoxin — NADP reductase, adrenodoxin reductase as well as more complex enzymes such as the mitochondrial NADH dehydrogenase and xanthine dehydrogenase. 

Many xenobiotics, including a wide variety of quinones and nitro compounds, will accept an electron from almost any redox flavoenzyme. The microsomal reduction of nitroaromatic compounds, quinones, quinone-imines, some azoaromatic compounds, paraquat, and tetrazolium salts is catalyzed by NADPH-cytochrome P-450 reductase [44], One-electron transfer to these electron acceptors has been proved to be obligatory in the case of quinone and nitro compounds, and is probably obligatory in other cases as well. Therefore, a reduction of an aromatic compound by NADPH-cytochrome P-450 reductase can probably be assumed to form a free radical metabolite. In contrast, free radical formation by reductive dehalogenation is totally cytochrome P-450-dependent, with the reductase being inactive. 

The vast majority of flavoenzymes catalyze oxidation-reduction reactions in which one substrate becomes oxidized and a second substrate becomes reduced and the isoalloxazine ring of the flavin prosthetic group (Figure 1) serves as a temporary repository for the substrate-derived electrons. The catalytic reaction can be broken conveniently into two steps, a reductive half reaction (from the viewpoint of the flavin) and an oxidative half reaction. The flavin ring has great utility as a redox cofactor since it has the ability to exist as a stable semiquinone radical. Thus, a flavoenzyme can oxidize an organic substrate such as lactate by removal of two electrons and transfer them as a pair to a 2-electron acceptor such as molecular oxygen, or individually to a 1-electron acceptor such as a cytochrome. 

Flavins are unique coenzymes that are able to catalyze both one- and two-electron transfers. Because of this, many flavoproteins are involved in transferring electrons between other proteins. Often, flavoproteins are reduced by two-electron donors, such as pyridine nucleotides, and then pass those electrons one at a time to a single-electron acceptor, such as an iron-sulfur cluster in another protein. Conversely, some enzymes accept single electrons from reduced enzymes. In either case, the flavoenzymes are transferring single electrons thus, flavin semiquinone is frequently stabilized and observed during turnover. 

Figure 11.9 Flavoenzyme catalyzed electron transfer and oxidation/oxygenation reactions The extensive conjugation of the isoaUoxazine ring system results in the yellow chromophore ( ax = 450 nm) in the oxidized flavin. Flavin semiquinones are stable radicals, because the unpaired electron is highly delocalized through the conjugated isoaUoxazine structure. The neutral semiquinone is blue = 570 nm) and the flavosemiquinone anion is red (A ax = 480 nm). The...

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... 

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