Flavins complexation with

As its name implies, this complex transfers a pair of electrons from NADH to coenzyme Q a small, hydrophobic, yellow compound. Another common name for this enzyme complex is NADH dehydrogenase. The complex (with an estimated mass of 850 kD) involves more than 30 polypeptide chains, one molecule of flavin mononucleotide (FMN), and as many as seven Fe-S clusters, together containing a total of 20 to 26 iron atoms (Table 21.2). By virtue of its dependence on FMN, NADH-UQ reductase is a jlavoprotein. 

Tu, S.-C. (1979). Isolation and properties of bacterial luciferase-oxygenated flavin intermediate complexed with long-chain alcohols. Biochemistry 18 5940-5945. 

Electrochemistry of transition metal complexes with flavins, nucleosides and their constituent bases. M. J. Clarke, Rev. Inorg. Chem., 1980, 2, 27-51 (56). 

We have not so far mentioned the Phase III increase in the Rapid signal (Fig. 5). It seems (67) that Phase II represents over reduction of molybdenum to Mo(IV), possibly by substrate radicals (see Section V H). The system then comes towards thermodynamic equilibrium by interaction between reduced active enzyme molecules and oxidized inactive ones (67, cf. 64). As Mo(IV) of the former is oxidized to Mo(V), during Phase III, so iron or flavin of the inactive enzyme is reduced. Later, in Phase IV, molybdenum of the inactive enzyme is reduced also to give the Slow signed. Alloxanthine, which as noted above, forms a stable complex with Mo(IV), seems to abolish both the slow phase in the 450 nm bleaching of the enzyme by xanthine and the Phase III increase in Rapid signal (91). 

Fig. 6. Difference spectra between xanthine oxidase inactivated with various pyra-zolo [3, 4-d] pyrimidines and the native enzyme. The spectra are believed to represent the increase in absorption occurring when Mo(VI) of native enzyme is converted to Mo(IV) complexed with the inhibitors. Spectra were obtained by treating the enzyme with inhibitors in the presence of xanthine, then admitting air, so as to re-oxidize the iron and flavin chromophores. The extinction coefficients, de, are expressed per mole of enzyme flavin. Since some inactivated enzyme was present, extinction coefficients per atom of molybdenum of active enzyme will be about 30% higher than these values. (Reproduced from Ref. 33, with the permission of Dr. V. Massey.)...

Voropai ES, Samtsov MP, Kaplevskii KN, Maskevich AA, Stepuro VI, Povarova OI, Kuznetsova IM, Turoverov KK, Fink AL, Uverskii VN (2003) Spectral properties of thio-flavin T and its complexes with amyloid fibrils. J Appl Spectrosc 70(6) 868-874... 

The reaction can be coupled to the oxidation of either NADH or NADPH by the presence of a flavin dehydrogenase, which is usually present complexed with the luciferase ... 

A long-known characteristic of D-amino acid oxidase is its tendency to form charge-transfer complexes with amines, complexes in which a nonbonding electron has been transferred partially to the flavin. Complete electron transfer would yield a flavin radical and a substrate radical which could be intermediates in a free radical mechanism, as discussed in the next section.256... 

Figure 15-11 Stereoscopic view of the benzoate ion in its complex with D-amino acid oxidase. A pair of hydrogen bonds binds the carboxylate of the ligand to the guanidinium group of R283. Several hydrogen bonds to the flavin ring of the FAD are also indicated. Courtesy of Retsu Miura.161...

The presence of metal ions in many flavoproteins suggested a direct association of metal ions and flavins. Although oxidized flavins do not readily bind most metal ions, they form red complexes with Ag+ and Cu+ with a loss of a proton from N-3.278 Flavin semiquinone radicals also form strong red complexes with many metals.264 If the complexed metal ion can exist in more than one oxidation state, electron transfer between the flavin and a substrate could take place through the metal atom. However, chelation by flavins in nature has not been observed. Metalloflavoproteins probably function by having the metal centers close enough to the... 

The catalytic effect of metal ions such as Mg2+ and Zn2+ on the reduction of carbonyl compounds has extensively been studied in connection with the involvement of metal ions in the oxidation-reduction reactions of nicotinamide coenzymes [144-149]. Acceleration effects of Mg2+ on hydride transfer from NADH model compounds to carbonyl compounds have been shown to be ascribed to the catalysis on the initial electron transfer process, which is the rate-determining step of the overall hydride transfer reactions [16,87,149]. The Mg2+ ion has also been shown to accelerate electron transfer from cis-dialkylcobalt(III) complexes to p-ben-zoquinone derivatives [150,151]. In this context, a remarkable catalytic effect of Mg2+ was also found on photoinduced electron transfer reactions from various electron donors to flavin analogs in 1984 [152], The Mg2+ (or Zn2+) ion forms complexes with a flavin analog la and 5-deazaflavins 2a-c with a 1 1 stoichiometry in dry MeCN at 298 K [153] ... 

This electron transport and proton flow is controlled by at least three other proteins on the cytosolic side of the membrane, P47, P67, and P21rac (Figure 5). Note that this is a much simpler enzyme complex than the complex III (cyt bc ) of mitochondria which drives proton export from the interior of mitochondria based on quinol oxidation. Despite its simplicity, the neutrophil enzyme may have similarities to the complex three, since it essentially carries out an oxidation of a protonated two electron flavin by a nonprotonated cytochrome b complex with two heme sites. This is the essence of the mitochondrial enzyme in that the two electron quinol is oxidized by a cytochrome b with two heme components. 

Flavin mononucleotide (FMN)-adenosine and flavin adenine dinucleotide (FAD)-adenosine complexes show quenched triplet lifetimes compared to FMN alone, which is cited as evidence of intramolecular com-plexation between the flavins and adenosine by Shiga and Piette [142]. Adenosine phosphates also form complexes with FAD [143]. The com-plexation between a flavin and adenosine is identical to the intermolecular complexing of adenosine and flavin moieties, in the latter case enforced by hydrophobic bonding [144-146]. Rath and McCormick [147] have examined the riboflavin complexes of a series of purine ribose derivatives... 

Mieloszyk and colleagues [226] determined that flavins which form charge-transfer complexes with proteins exist in both the ground and excited electronic states. In the flavin-riboflavin-binding protein the trytophan is considered to be the donor. Other such complexes of flavin coenzymes and apoenzymes are known [227-229]. 

Trivalent hydrogen-bonding systems have been used very extensively for guiding and influencing the structuring of polymers. As mentioned in Sect. 1, Fig. 5, the most important triple-hydrogen bonds derive from 2,6-diamino-pyridines, 2,6-diamino-1,3,5-triazines and their complexes with flavine- and... 

Whereas many coenzymes form noncovalent complexes with their respective apoenzymes, various flavoenzymes are characterized by covalently bound FMN (25) or FAD (Fig. 3). Covalent linkage involves the position 8a methyl group or the benzenoid carbon atom 6 of the flavin and a cysteine or histidine residue of the protein. The covalent CN or CS bond can be formed by autoxidation of the noncovalent apoen-zyme/coenzyme precursor complex as shown in detail for nicotine oxidase (59). 

Figure 1 Catalytic cycle of p-hydroxybenzoate hydroxylase. In the first step, pOHB and NADPH bind (k- ) and the FAD becomes reduced (l<2). NADP is released (l<3) and O2 reacts (l<4) to form the C4a-hydroperoxy-FAD (E FIHOOH-S) in complex with substrate. Hydroxylation occurs via l<5 to yield the dienone form of product and the C4a-hydroxy-FAD (Int II). Tautomerization yields 3,4-dihydroxybenzoate in complex with the enzyme (E FI HOH-P). Dissociation of 3,4-DOHB and H2O via ky leads to free enzyme (E Flox). Uncoupling occurs via the loss of H2O2 from the C4a-hydropeoxy flavin (kg).

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