Flavin adenine dinucleotide synthesis in animal tissues

DeLuca, Chester; Kaplan, Nathan O.

doi:10.1016/0006-3002(58)90233-6

Cited by 48 publications

(10 citation statements)

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“…8 and references therein). Overcoming the assumption of an exclusive cytosolic localization for the enzymes responsible for FAD synthesis sustained by many laboratories (13,14,16,17), we first proposed a mitochondrial localization for FADS both in rat liver and in mammalian cell lines (BHK-21 and Caco-2) transiently expressing hFADS1 (18,19,23,53).…”

Section: Discussionmentioning

confidence: 99%

FAD Synthesis and Degradation in the Nucleus Create a Local Flavin Cofactor Pool

Giancaspero

Busco

Panebianco

et al. 2013

Journal of Biological Chemistry

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Background: FAD synthase is known to catalyze the biosynthesis of FAD in cytosol and mitochondria. Results: The existence of a nuclear FAD synthase and a FAD-hydrolyzing activity is demonstrated. Conclusion: A dynamic pool of FAD exists in the nucleus. Significance: Nuclear, mitochondrial, and cytosolic FAD synthase pools constitute a flavin network involved in the regulation of cellular metabolism and epigenetic events.

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Section: Discussionmentioning

confidence: 99%

FAD Synthesis and Degradation in the Nucleus Create a Local Flavin Cofactor Pool

Giancaspero

Busco

Panebianco

et al. 2013

Journal of Biological Chemistry

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“…Enzymatic synthesis of FAD was first shown to occur in the cytosol of rat liver (21). Synthesis of FAD from externally added riboflavin or FMN has subsequently provided evidence for riboflavin kinase and FAD synthetase activities in mitochondria in Saccharomyces cerevisiae (22,23) and rat liver (24,25).…”

mentioning

confidence: 99%

Flavin Nucleotide Metabolism in Plants

Sandoval¹,

Zhang²,

Roje³

2008

Journal of Biological Chemistry

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FAD synthetases (EC 2.7.7.2) catalyze biosynthesis of FAD from FMN and ATP. Monofunctional FAD synthetases are known to exist in mammals and yeast; bifunctional enzymes also catalyzing phosphorylation of riboflavin to FMN are known to exist in bacteria. Previously known eukaryotic enzymes with FAD synthetase activity have no sequence similarity to prokaryotic enzymes with riboflavin kinase and FAD synthetase activities. Proteins homologous to bacterial bifunctional FAD synthetases, yet shorter and lacking amino acid motifs at the C terminus, were found by bioinformatic analyses in vascular plant genomes, suggesting that plants contain a type of FAD synthetase previously known to exist only in prokaryotes. The Arabidopsis thaliana genome encodes two of such proteins. Both proteins, which we named AtRibF1 and AtRibF2, carry N-terminal extensions with characteristics of organellar targeting peptides. AtRibF1 and AtRibF2 cDNAs were cloned by reverse transcription-PCR. Only FAD synthetase activity was detected in the recombinant enzymes produced in Escherichia coli. FMN and ATP inhibited both enzymes. Kinetic parameters of AtRibF1 and AtRibF2 for the two substrates were similar. Confocal microscopy of protoplasts transformed with enhanced green fluorescence protein-fused proteins showed that AtRibF1 and AtRibF2 are targeted to plastids. In agreement with subcellular localization to plastids, Percoll-isolated chloroplasts from pea (Pisum sativum) synthesized FAD from imported riboflavin. Riboflavin kinase, FMN hydrolase, and FAD pyrophosphatase activities were detected in Percoll-isolated chloroplasts and mitochondria from pea. We propose from these new findings a model for subcellular distribution of enzymes that synthesize and hydrolyze flavin nucleotides in plants.FMN and FAD are essential cofactors for a variety of enzymes that participate in many metabolic processes in all organisms. In plants, these cofactors are required for photosynthesis, mitochondrial electron transport, fatty acid oxidation, photoreception, DNA repair, metabolism of other cofactors, and biosynthesis of many secondary metabolites. Metabolism of FMN and FAD includes reactions that synthesize and hydrolyze these flavin nucleotides. Enzymes catalyzing flavin nucleotide biosynthesis and hydrolysis, and their subcellular localization, are incompletely understood in plants and in other organisms.Phosphorylation of riboflavin to FMN and adenylylation of FMN to FAD are, respectively, catalyzed by the enzymes riboflavin kinase (EC 2.7.1.26) and FAD synthetase (EC 2.7.7.2) in the presence of ATP and Mg 2ϩ . These enzymes have been found in prokaryotes and eukaryotes.In prokaryotes, bifunctional enzymes with riboflavin kinase and FAD synthetase activities (1-5), and monofunctional enzymes with only riboflavin kinase activity (6, 7) have been described. No monofunctional FAD synthetases have yet been found in prokaryotes. Bioinformatic evidence suggests that the bifunctional enzymes are prevalent among the prokaryotic species sequenced to date (8).In ma...

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“…A similar pathway for synthesis of flavinadenine dinucleotide was reported in a riboflavin-secreting mutant yeast (Giri & Krishnaswamy, 1956). Recently Deluca & Kaplan (1958) showed that synthesis of flavinadenine dinucleotide occurs in rat-liver supernatants.…”

Section: (Received 15 July 1959)mentioning

confidence: 99%