Riboflavin flavin adenine dinucleotide synthesis

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. 

In bacteria, flavin adenine dinucleotide (FAD) is the prosthetic group of the photolyases that catalyze reductive repair of light-induced pyrimidine dimers in DNA. Riboflavin is the light-emitting molecule in some bioluminescent fungi and bacteria, and is the precursor for synthesis of the dimethylbenzimidazole ring of vitamin B12 (Section 10.7.3). 

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. 

These reactions lead to a synthesis of cozymase or flavine -adenine dinucleotide from adenosine triphosphate with nicotinamide-ribofuranoside-5-phosphoric acid or riboflavine phosphate respectively. 

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. 

The mechanism of synthesis of the coenzyme forms of riboflavin has been studied by a number of investigators. Purified enzymes capable of catalyzing the formation from riboflavin of riboflavin 5 -phosphate and flavin adenine dinucleotide have been described. The formation of a number of glycoades of riboflavin by animal tissue preparations and microorganisms has been reported. 

Until recently the synthesis of flavin adenine dinucleotide had not been studied with purified enzymes from animal tissues. However, the ability of animal tissues to synthesize this coenzyme has been known for a number of years. Klein and Kohn 138) observed formation of flavin adenine dinucleotide in red blood cells in vivo and in vitro, and Trufanov 139) obtained synthesis of flavin adenine dinucleotide in rat tissue slices. Makino et al. 130) obtained formation of flavin adenine dinucleotide from vitamin Ba and ATP in the presence of pig kidney acetone powders, and Yagi 129) reported the synthesis of the coenzyme by the action of acetone powders of rabbit liver or kidney from riboflavin 5 -phosphate, but not riboflavin, and ATP. 

It was not certain from the above observations whether the synthetis of flavin adenine dinucleotide in animal tissues proceeded by the same mechanism as that demonstrated with the purified enzyme from yeast. The demonstration by Watarai et al. 140) that flavin adenine dinucleotide synthesized from riboflavin 5 -phosphate-P and ATP in rabbit liver homogenates had the same molar specific radioactivity as added riboflavin 5 -phosphate-P would be in accord with a flavin adenine dinucleotide-pyrophosphorylase reaction, but suffered from the lack of demonstration of net synthesis of the coenzyme in the system. 

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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