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6.7- Dimethyl-8-ribityllumazine

Figure 25-20 The biosynthesis of riboflavin and of the dimethylbenzimidazole group of vitamin B12. The fact that two molecules of 6,7-dimethyl-8-ribityllumazine disproportionate to form riboflavin accounts for the need for two molecules of each reactant and product in many steps. Figure 25-20 The biosynthesis of riboflavin and of the dimethylbenzimidazole group of vitamin B12. The fact that two molecules of 6,7-dimethyl-8-ribityllumazine disproportionate to form riboflavin accounts for the need for two molecules of each reactant and product in many steps.
Soon afterward, it was shown that 6,7-dimethyl-8-ribityllumazine (10) was an intermediate in the biosynthesis of riboflavine it was noted that the UV spectrum of this lumazine could not be reconciled with those of... [Pg.123]

Even prior to the elucidation of the first committed step of the riboflavin pathway, it had been shown that the benzenoid ring of riboflavin is assembled from two identical 4-carbon precursors. More specifically, the final step in the biosynthesis of the vitamin involves a dismutation of 6,7-dimethyl-8-ribityllumazine (6), where one of the substrate molecules serves as donor and the other as acceptor of a 4-carbon segment.19,20 6,7-Dimethyl-8-ribityllumazine, in turn, is formed in the penultimate step of the biosynthetic pathway from 5-amino-6-ribitylamino-4(3f/)-pyrimidinedione (3), an intermediate that is obtained from the product of GTP cyclohydrolase II by a sequence of deamination, side chain reduction, and dephosphorylation (Figure 3). The nature of the 4-carbon precursor required for the formation of 6,7-dimethyl-8-ribityllumazine (6) from 5-amino-6-ribitylamino-4(3f/)-pyrimidinedione (3) remained controversial for quite a long period, with working hypotheses including, but not limited to, tetroses, pentoses, and acetoin. [Pg.682]

Early work on flavinogenic ascomycetes by Masuda afforded a green fluorescent substance (initially designated G-compound), which was identified as 6,7-dimethyl-8-ribityllumazine that is structurally similar to riboflavin, although the benzenoid ring is missing.Subsequent work showed that the compound could be... [Pg.3]

Subsequent to the identification of 3,4-dihydroxy-2-butanone 4-phosphate (8) as the 4-carbon precursor of 6,7-dimethyl-8-ribityllumazine in the late 1980s,it was not difficult to show that the j3 subunits catalyzed the condensation of 6 with 8 under formation of the lumazine derivative 9. The heavy riboflavin synthase can now be correctly addressed as a riboflavin synthase/lumazine synthase complex. However, the designation /3 subunit of riboflavin synthase clung tenaciously to the 16 kDa peptide that had ultimately been assigned a function as lumazine synthase (reaction VIII in Figure 1) notably, this somewhat unfortunate nomenclature survives in databases, despite the fact that in most organisms, lumazine synthase and riboflavin synthase (reaction IX in Figure 1) are separate proteins. [Pg.12]

Steady-state kinetic analysis afforded evidence for intermediate channeling in the lumazine synthase/ riboflavin synthase complex. Briefly, the conversion of 6,7-dimethyl-8-ribityllumazine molecules that have been newly formed by the lumazine synthase module of the protein complex are more rapidly converted to riboflavin than molecules from the bulk solvent. The topological constraint by the capsid is believed to cause this phenomenon. It has been proposed that the channels along the five-fold axes could serve as port of entry and exit for substrates and products. ... [Pg.15]

It is generally assumed that the unusual CH acidity of 6,7-dimethyl-8-ribityllumazine is important for the understanding of the enzyme-catalyzed as well as the uncatalyzed reaction. Briefly, the position 7 methyl groups of 8-substituted 7-methyllumazine have pA values in the range of 8—9. " The anions are characterized by their 7-exomethylene structure. In cases where the position 8 substituent carries hydroxyl groups in the 2 or 3 position, a nucleophilic attack of C-7 of the exomethylene anion by the hydroxyl group is conducive to the formation of tricylic systems (Figure 9). [Pg.15]

Specifically, an alkaline aqueous solution of 6,7-dimethyl-8-ribityllumazine contains a mixture of at least five anionic species, namely the exomethylene-type anion with an open chain structure of the position 8 substituent and two diastereomers each of the 5-ring and 6-ring forms arising by intramolecular reaction of the 2 and 3 hydroxyl groups. The hypothesis of an involvement of one of the tricyclic species as intermediates in the biosynthesis of riboflavin is not supported by more recent data. The exomethylene form appears likely to be a late intermediate in the mechanism of lumazine synthase as documented by stopped flow analysis. Moreover, the exomethylene form (31) has been proposed as an early intermediate of the riboflavin synthase reaction. This is supported by the early observation that riboflavin synthase accelerates proton exchange at the position 7 methyl group. [Pg.16]

An isotope effect of 5.0 has been found for [6a- H3]6,7-dimethyl-8-ribityllumazine. Hence, the release of a proton(s) from the position 6 methyl group could involve a relatively high energy barrier. " ... [Pg.16]

While the stereochemically favored addition of a 2 or 3 hydroxyl group to C-8 of 6,7-dimethyl-8-ribityllumazine has been documented in considerable detail, the formation of a position 7 hydrate has only been observed after the introduction of fluorine to increase the electronegativity. Indeed, the bistrifluromethyl-8-ribityllumazine is so stable that the two diastereomeric forms A and B show no evidence of racemization whatsoever. Notably, a hypothetical covalent hydrate of 6,7-dimethyl-8-ribityllumazine has been proposed as an intermediate at the donor site of riboflavin synthase. " ... [Pg.16]

NMR spectroscopy of multiply C-labeled Compound ( samples (obtained by rapid quench experiments with various C-labeled samples of 6,7-dimethyl-8-ribityllumazine) revealed the pentacyclic structure 36 that is clearly an adduct of two 6,7-dimethyl-8-ribityllumazine (9) molecules (Figures 10 and 11). The optical absorption of the compound is well in line with the presence of a lumazine motif and a pyrimidine motif... [Pg.17]

Compound Q can be converted by riboflavin synthase into a mixture of 6,7-dimethyl-8-ribityllumazine, riboflavin, and 5-amino-6-ribitylamino-2,4(l//,3f/)-pyrimidinedione. " This is best explained by the hypothesis that Compound Q is an intermediate of the enzyme-catalyzed reaction than can undergo either a forward reaction affording riboflavin (10) and 6 or a reverse reaction affording 6,7-dimethyl-8-ribityllumazine (9) with similar reaction velocity. Moreover, it was shown by presteady-state kinetic analysis that Compound (X fulfills the criteria for a kinetically competent reaction intermediate. As described in more detail below, it can be deduced from X-ray structure data that the two lumazine components in the pentacyclic adduct 36 must be fused in cis. ... [Pg.17]

Figure 11 Optical spectra of Compound Q (a) and 6,7-dimethyl-8-ribityllumazine (b) at pH 3.4 (solid lines), pH 8.8 (dashed lines), and pH 11.1 (dotted lines). Figure 11 Optical spectra of Compound Q (a) and 6,7-dimethyl-8-ribityllumazine (b) at pH 3.4 (solid lines), pH 8.8 (dashed lines), and pH 11.1 (dotted lines).
Figure 15 Active site of riboflavin synthase of Schizosaccharomyces pombe formed by two adjacent monomers with bound 6-carboxyethyl-7-oxo-8-ribityllumazine (37). (a) The ligand bound to the N barrel (red) is drawn in yellow, whereas the 6-carboxyethyl-7-oxo-8-ribityllumazine in the adjacent C barrel (blue) is shown in dark yellow, (b) Proposed binding of 6,7-dimethyl-8-ribityllumazine at the active site, (c) Model for the pentacyclic reaction intermediate. ... Figure 15 Active site of riboflavin synthase of Schizosaccharomyces pombe formed by two adjacent monomers with bound 6-carboxyethyl-7-oxo-8-ribityllumazine (37). (a) The ligand bound to the N barrel (red) is drawn in yellow, whereas the 6-carboxyethyl-7-oxo-8-ribityllumazine in the adjacent C barrel (blue) is shown in dark yellow, (b) Proposed binding of 6,7-dimethyl-8-ribityllumazine at the active site, (c) Model for the pentacyclic reaction intermediate. ...
Up to now, this 1 MDa protein has been observed only in Bacillaceae. Computer modeling has confirmed that the central cavity of the icosahedral capsid is large enough to accommodate the riboflavin synthase trimer (Figure 16). However, there are no corresponding symmetry properties between the two modules that could suggest a potential orientation. The molecular structure is not known in closer detail. The import and export of substrates and products is also an open problem. It is hard to see how the channels in the capsid wall could allow the passage of 6,7-dimethyl-8-ribityllumazine, and, even less, of riboflavin. Dynamic fluctuations of the capsid structure have been proposed but remain speculative. [Pg.21]

Intermediate channeling resp. substrate channeling has been reported for heavy riboflavin synthase. At low substrate concentrations, 6,7-dimethyl-8-ribityllumazine formed in situ by the lumazine synthase capsid is more rapidly converted by the resident riboflavin synthase as compared to 6,7-dimethyl-8-ribityllumazine in the bulk solvent. Retarded evasion of the newly formed lumazine synthase product from inside the capsid has been proposed as a tentative explanation. [Pg.22]

In vivo studies with C-labeled precursors established that Archaea generate riboflavin via 6,7-dimethyl-8-ribityllumazine. A protein with riboflavin synthase activity was purified from Methanothermobacter thermoautotrophicus, and the cognate gene was cloned by a marker rescue strategy. The peptide of 154 amino acid residues showed no intramolecular sequence similarity and no sequence relationships with the riboflavin synthases of eubacteria and eukarya. [Pg.22]

While the riboflavin synthases of Archaea are devoid of similarity with those of eubacteria and eukaryotes, they have significant sequence similarity with 6,7-dimethyl-8-ribityllumazine synthases (Figure 17). ... [Pg.22]

Dimethyl-8-ribityllumazine synthase and the pentameric, archaeal riboflavin synthase appear to have diverged from a common ancestor at an early time point in the evolution of Archaea. Genes that may specify riboflavin synthases of the eubacterial type in a few Archaea may have been acquired relatively recently by horizontal gene transfer. [Pg.22]

Figure 19 Stereochemistry of 6,7-dimethyl-8-ribityllumazine conversion into riboflavin catalyzed by eubacterial (trimeric) and archaeal (pentameric) riboflavin synthase (R, ribityl). Figure 19 Stereochemistry of 6,7-dimethyl-8-ribityllumazine conversion into riboflavin catalyzed by eubacterial (trimeric) and archaeal (pentameric) riboflavin synthase (R, ribityl).
G. W. Plaut R. L. Beach, Interaction of Riboflavine Synthetase with Analogs of 6,7-Dimethyl-8-Ribityllumazine. In Chemistry and Biology of Pteridines, Proceedings of the 5th International Symposium 1975 W. Pfieiderer, Ed. de Gruyter Berlin pp 101-124. [Pg.34]

The second finding was that the pentacyclic intermediates formed by the trimeric E. coli enzyme and the pentameric M. jannaschii riboflavin synthase are diastereomers, as shown in Figure 19. These pentacyclic diastereomers are formed by the condensation of two molecules of 6,7-dimethyl-8-ribityllumazine with the same regiochemistry in both enzymes. " This difference clearly results from the fact that these are different enzymes with different active sites. Each of the diastereomers is a catalytically competent intermediate for its respective enzyme but does not serve as a substrate for the other enzyme. ... [Pg.733]

The intermediate 5-amino-6-ribitylamino-2,4(I//,3//)-pyrimidinedione 5 -phos phate 50 is dephosphorylated through an unknown process, forming 5-amino-6-ribitylamino-2,4(l//,3//)-pyrimidinedione 52. The latter is converted into 6,7-dimethyl-8-ribityllumazine 53 by a lumazine synthase or riboflavin synthase P-chain, nfeH, through condensation with 3,4-dihydroxy-2-butanone 4-phosphate 54 obtained from ribulose 5-phosphate. The final step involves the unusual dismutation of 6,7-dimethyl-8-ribityllumazine 53, catalyzed by riboflavin synthase or riboflavin synthase a-chain, n feB, affording riboflavin and the dephosphorylated biosynthetic intermediate 52. Riboflavin is then converted to the coenzyme forms FMN and FAD. [Pg.613]


See other pages where 6.7- Dimethyl-8-ribityllumazine is mentioned: [Pg.110]    [Pg.308]    [Pg.93]    [Pg.1345]    [Pg.1462]    [Pg.93]    [Pg.102]    [Pg.93]    [Pg.102]    [Pg.15]    [Pg.17]    [Pg.17]    [Pg.20]    [Pg.121]    [Pg.148]    [Pg.156]    [Pg.733]    [Pg.432]    [Pg.549]    [Pg.102]    [Pg.102]    [Pg.411]    [Pg.528]   
See also in sourсe #XX -- [ Pg.1462 ]




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6.7- Dimethyl-8-ribityllumazine structure

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