Flavin adenine dinucleotide reduced , structure

This thiol-disulfide interconversion is a key part of numerous biological processes. WeTJ see in Chapter 26, for instance, that disulfide formation is involved in defining the structure and three-dimensional conformations of proteins, where disulfide "bridges" often form cross-links between q steine amino acid units in the protein chains. Disulfide formation is also involved in the process by which cells protect themselves from oxidative degradation. A cellular component called glutathione removes potentially harmful oxidants and is itself oxidized to glutathione disulfide in the process. Reduction back to the thiol requires the coenzyme flavin adenine dinucleotide (reduced), abbreviated FADH2. 

Scheme 2. Structures of oxidized (FAD) and reduced (FADH2) forms of flavin adenine dinucleotide.

Flavin adenine dinucleotide (FAD) and its reduced form dihydroflavin (FADH2) participate in a large number of oxidation/reduction reactions in metabolism150. The structure of the reduced form has a distinct enamine feature that has been hypothesized to participate in covalent bonds with a number of substrates. 

Photoreactivating enzyme contains two chromophores. (A chromophore is a structural moiety that absorbs light of characteristic wavelengths.) One chromophore is flavin adenine dinucleotide in the reduced state, FADH". The second chromophore in some photolyases is 5,10-methenyltetrahydrofolate and in others is 8-hydroxy-5-deazaflavin. 

FIGURE 15.4 The structures of riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD). Even in organisms that rely on the nicotinamide coenzymes (NADH and NADPH) for many of their oxidation-reduction cycles, the flavin coenzymes fill essential roles. Flavins are stronger oxidizing agents than NAD and NADP. They can be reduced by both one-electron and two-electron pathways and can be reoxidized easily by molecular oxygen. Enzymes that use flavins to carry out their reactions—flavoenzymes—are involved in many kinds of oxidation-reduction reactions. 

Xanthine oxidase can reduce nitrate to nitrite (Westerfield et al. 1959, Fridovich and Handler 1962). Xanthine oxidase and dissimilatory nitrate reductase share structural similarities. Both are molybdoenzymes and contain flavin adenine dinucleotide and Fe/S clusters (McCord 1985, Mitchell 1986, Payne et al. 1997). Zhang et al. (1998) reported that both purified bovine buttermilk xanthine oxidase and xanthine oxidase-containing inflamed human synovial tissue can generate NO by reducing nitrite in the presence of NADH. This nitrite reductase activity of xanthine oxidase may act as a supplement to the activity of nitric oxide synthase (NOS) to redistribute blood flow to ischaemic tissues when NOS activity is absent. 

NADH cytochrome c reductase was isolated from pigeon breast and pig heart muscle. The enzyme was shown to contain four atoms of iron per flavin molecule. NADH cytochrome c reductase, like succinic dehydrogenase, is a ferroflavoprotein. The ratio of iron to flavin is four. The enzyme contains sulfhydryl groups that can be titrated by classical methods, but their oxidation has no effect on the enzymatic activity. In contrast, the removal of the metal leads to a decrease in the ability of the enzyme to reduce cytochrome c. As for succinic dehydrogenase, the structure of the flavin in NADH cytochrome c reductase is not clear. It was demonstrated that it is not flavin mononucleotide, but the identity of the flavin component with flavin adenine dinucleotide is not established in fact, the flavin component differs from the classical FAD by its chromatographic properties and its behavior in enzymic assays. It is not known if it is a structural variation of the flavin nucleotide or if the nucleotide is conjugated to a peptide. 

Figure 1 Structural formulae of riboflavin, FMN, and FAD (1) riboflavin in oxidized (FL j) or reduced form (FL, ) (2) FMN, flavin mononucleotide (3) FAD, flavin adenine dinucleotide. ...

Fig. 2.8. Structure of flavin adenine dinucleotide (FAD) (a) oxidized form (FAD) (b) reduced form (FADH2)...

Next we tested biologically relevant electron acceptors. EGFP oxidative redding was found to occur in the presence of cytochrome c (ref. 15), flavin adenine dinucleotide (FAD, 6), flavin mononucleotide (FMN, 7), the FAD-containing flavoprotein ucose oxidase (which belongs to the same structural class as ubiquitous and abundant enzymes of cell redox homeostasis, such as glutathione reductase and thioredoxin reductase ) and nicodnamide adenine dinucleotide (NAD, 8). So, excited EGFP was able to reduce... 

The second type of biological electron transfer involves a variety of small molecules, both organic and inorganic. Examples of these are (a) nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) as two electron carriers and (b) quinones and flavin mononucleotide (FMN), which may transfer one or two electrons. The structure of NAD and its reduced counterpart NADH are shown in Figure 1.12. 

In 1989, BH4 was found to be a cofactor for nitric oxide synthase (NOS) [ 126, 127]. BH4 is also involved in dimerization of NOS, as NOS is catalytically active in a homodimer structure. Three isoforms of NOS exist neuronal NOS (NOS 1), inducible NOS (NOS 2) and endothelial NOS (NOS 3). BH4 is essential for all NOS isoforms. The NOS isoforms share approximately 50-60% sequence homology. Each NOS polypeptide is comprised of oxygenase and reductase domains. An N-terminal oxygenase domain contains iron protoporphyrin IX (heme), BH4 and an arginine binding site, and a C-terminal reductase domain contains flavin mononucleotide (FMN), and a reduced nicotin-amide adenine dinucleotide phosphate (NADPH) binding site. 

Electron-transfer (ET) reactions play a central role in all biological systems ranging from energy conversion processes (e.g., photosynthesis and respiration) to the wide diversity of chemical transformations catalyzed by different enzymes (1). In the former, cascades of electron transport take place in the cells where multicentered macromolecules are found, often residing in membranes. The active centers of these proteins often contain transition metal ions [e.g., iron, molybdenum, manganese, and copper ions] or cofactors as nicotinamide adenine dinucleotide (NAD) and flavins. The question of evolutionary selection of specific structural elements in proteins performing ET processes is still a topic of considerable interest and discussion. Moreover, one key question is whether such stmctural elements are simply of physical nature (e.g., separation distance between redox partners) or of chemical nature (i.e., providing ET pathways that may enhance or reduce reaction rates). 

ACP = acyl carrier protein ACPA D = ACPA desat-urase AlkB = octane 1-monooxygenase AOX = alternative oxidase DMQ hydroxylase = 5-demethoxyquinone hydroxylase EXAFS = extended X-ray absorption fine structure spectroscopy FMN = flavin mononucleotide FprA = flavoprotein A (flavo-diiron enzyme homologue) Hr = hemerythrin MCD = magnetic circular dichroism MME hydroxylase = Mg-protophorphyrin IX monomethyl ester hydroxylase MMO = methane monooxygenase MMOH = hydroxylase component of MMO NADH = reduced nicotinamide adenine dinucleotide PAPs = purple acid phosphatases PCET = proton-coupled electron transfer, PTOX = plastid terminal oxidase R2 = ribonucleotide reductase R2 subunit Rbr = rubrerythrin RFQ = rapid freeze-quench RNR = ribonucleotide reductase ROO = rubredoxin oxygen oxidoreductase XylM = xylene monooxygenase. 

Ghisla, S., and S. G. Mayhew Identification and Structure of a Novel Flavin Prosthetic Group Associated with Reduced Nicotinamide Adenine Dinucleotide from Peptostreptococcus elsdenii. J. Biol. Chem. 248, 6568 (1973). 

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