Flavin mononucleotide synthesis

Flavin mononucleotide was first isolated from the yellow en2yme in yeast by Warburg and Christian in 1932 (4). The yellow en2yme was spHt into the protein and the yellow prosthetic group (coen2yme) by dialysis under acidic conditions. Flavin mononucleotide was isolated as its crystalline calcium salt and shown to be riboflavin-5Lphosphate its stmeture was confirmed by chemical synthesis by Kuhn and Rudy (94). It is commercially available as the monosodium salt dihydrate [6184-17 /, with a water solubiUty of more than 200 times that of riboflavin. It has wide appHcation in multivitamin and B-complex solutions, where it does not require the solubili2ers needed for riboflavin. 

Riboflavin, or vitamin B2, is a constituent and precursor of both riboflavin 5 -phosphate, also known as flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD). The name riboflavin is a synthesis of the names for the molecule s component parts, ribitol and flavin. The structures of riboflavin. 

Flavin mononucleotide (FMN), 25 796 cofactor regeneration using, 3 673 Flaviviruses, 3 137-138 Flavones, microwave-assisted synthesis of, 16 575... 

Synthesis of NO Arginine, 02, and NADPH are substrates for cytosolic NO synthase (Figure 13.9). Flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), heme, and tetrahydro- biopterin are coenzymes for the enzyme, and NO and citrulline are products of the reaction. Three NO synthases have been identified. Two are constitutive (synthesized at a constant rate regardless of physiologic demand), Ca2+-calmodulin-dependent enzymes. They are found primarily in endothelium (eNOS), and neural tissue... 

Once the hexameric structure of the yeast FAS was established, the number of functional active sites still remained to be determined. Earlier studies had shown that the functional complex contains approximately six equivalents each of two prosthetic groups 4 -phosphopantetheine [60,63], necessary for the AGP functionality, and flavin mononucleotide [64], an essential component of the enoyl reductase activity. These studies provided an early indication that each of the six active sites in the complex has a full set of the chemical groups necessary for fatty acid synthesis. Nevertheless, conflicting reports appeared in the literature as to the competence of six active sites. Whereas some reports suggested the possibility of half-sites reactivity (only three of the six sites are catalytically competent) [65, 66], others proposed that all six active sites could synthesize fatty acids [62]. Subsequent active site titration experiments were performed which quantitated the amount of fatty acyl products formed in the absence of turnover [67]. Single-turnover conditions were achieved through the use of... 

Most of bacterial biosensors are based on the operon luxCDABE that codes for the bacterial luciferase founded in the marine bacteria V. fischeri and V. harveyi, and for an essential aldehyde substrate that would otherwise have to be supplied exogenously. The cluster luxAB cassette codes for the luciferase whereas luxCDE encodes a fatty acid reductase complex. The latter enzymes are responsible for the synthesis of the long-chain aldehyde that is required as substrate in the bioluminescence reaction (Meighen and Dunlap, 1993 Hakkila et al., 2002). Luciferase catalyses the oxidation reaction of flavin mononucleotide (FMNH2). A long-chain (7 to 16 carbons) aldehyde is reduced in presence of oxygen by the aldehyde reductase. The outcome of the bioluminescent reaction can be expressed as follows ... 

Other Coenzymes and Cofactors.— The chemical synthesis of riboflavin phosphates and their acetyl derivatives has been reinvestigated. Riboflavin 4 -monophosphate (10) is an important contaminant of commercial flavin mononucleotide (FMN), and... 

FIGURE I Role for calmodulin (CaM) in triggering interdomain electron transfer to the nitric oxide synthase (NOS) heme iron. Electrons derived from NADPH can transfer only into the flavin centers of CaM-free neuronal NOS (A). CaM binding to NOS occurs in response to elevated Ca concentrations, and this enables electrons to transfer from the flavins to the heme iron. Heme iron reduction is associated with increased NADPH oxidation and results in (B) superoxide (O2) production in the absence of L-arginine or (C) nitric oxide (NO) synthesis in the presence of L-arginine. FAD, Flavin-adenine dinucleotide FMN, flavin mononucleotide. 

FIGURE 2 Proposed dual mode for calmodulin (CaM) control of nitric oxide synthase (NOS) electron transfer. Neuronal NOS is composed of a reductase and an oxygenase domain, shown as two circles. CaM binding to NOS activates at two points in the electron transfer sequence (1) It increases the rate at which NADPH-derived electrons are transferred into the flavins, and (2) it enables the flavins to pass electrons to the oxygenase domain of NOS. Activation at the first point is associated with an increase in reductase domain-specific catalytic activities, such as electron transfer to cytochrome c or ferricyanide (FeCN ). Activation at the second point is associated with a reduction of NOS heme iron, an initiation of NO synthesis from L-arginine (Arg), or a reduction of Oj to form superoxide (O2) in the absence of substrate. FAD, Flavin-adenine dinucleotide FMN, flavin mononucleotide NO, nitric oxide. 

Synthesis oxidative electropolymerization of riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) in acid media [698],... 

Vitamin B2 is riboflavin (ll.lOSe), which is utilised for the synthesis of coenzymes flavin mononucleotide (riboflavin monophosphate) (FMN), and flavin adenine dinucleotide (FAD) (11.110) and (11.28). Riboflavin was isolated from yeast in 1932 [33]. 

A specific kinase, flavokinase, yields flavin mononucleotide in the presence of riboflavin and ATP, and probably magnesium. Schrecker and Kornberg [97] described an enzyme that catalyzes the synthesis of flavin adenine dinucleotide from flavin mononucleotide and ATP. The enzyme was isolated from yeast, and similar enzymes have been found in animal tissues. The enzyme is called flavin adenine dinucleotide pyrophosphorylase. 

Barile, M., Passarella, S., Bertoldi, A., and Quagliariello, E., 1993. Flavin adenine dinucleotide synthesis in isolated rat liver mitochondria caused by imported flavin mononucleotide. Archives of Biochemistry and Biophysics. 

FAD is similar in structure to DPN. It differs in that riboflavin replaces the nicotinamide riboside moiety. It is formed when red blood cells are incubated with riboflavin.A purified enzyme system from yeast catalyzes the synthesis of this coenzyme from ATP and flavin mononucleotide. ... 

More than 100 years ago a fluorescent compound was isolated first fi om whey, and later from different biological materials. When it Ijecame clear that the isolated yellow pigments, named lactochrome, ovoflavin, or lactoflavin, had a common structure, the new compound was named riboflavin (vitamin B2) (for historical review see 2). In the years between 1933 and 1935 the structure and the main chemical reactions of riboflavin were studied and the chemical synthesis was performed. Soon afterward, the coenzyme forms, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), were isolated in pure form, and the structures were determined. In the last 50 years many flavoproteins were isolated and their physicochemical properties were studied. Succinate dehydrogenase was the first enzyme found with the prosthetic group (FAD) covalently bound to the protein. About 20 flavoproteins are now known to contain covalently bound coenzyme (mainly via carbon atom 8a) (3). In mammalian tissue, the number of covalently bound flavoproteins appears to be limited. 

Non- oxidative branch Pentose-5 -Phosphates Ribose-5-P 2 deoxy ribose-5-P 5 -phosphoribosyl-1 -pyrophosphate (PRPP) i) Structural components of nucleotides a. Basal structural component of RNA b. Basal structural component of DNA c. Precursor of both de novo and salvage synthesis of nucleotides ii) Intermediate products of purine metabolism and act as precursor molecules of cofactors, e g., riboflavin, flavin mononucleotide (FMN), flavin adenine di nucleotide (FAD) iii) Precursor of the amino acid. Histidine. 

Riboflavin (vitamin B ) plays an essential role in cellular metabolism, being the precursor of the co-enzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) that both act as hydrogen carriers in biological redox reactions involving enzymes such as NADH dehydrogenase. Once riboflavin is absorbed in the human body, the synthesis of these flavin co-enzymes is controlled by thyroid hormones that regulate the activities of the flavin biosynthetic enzymes (Rucker et al. 2001). 

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