The metabolism of riboflavin is a tightly controlled process that depends on the riboflavin status of the individual. Riboflavin is converted to coenzymes within the cellular cytoplasm of most tissues but mainly in the small intestine, liver, heart, and kidney. The metabolism of riboflavin begins with the adenosine triphosphate (ATP)-dependent phosphorylation of the vitamin to flavin mononucleotide (FMN). Flavokinase, the catalyst for this conversion, is under hormonal control. FMN can then be complexed with specific apoenzymes to form a variety of flavoproteins; however, most is converted to flavin-adenine dinucleotide (FAD) by FAD synthetase. As a result, FAD is the predominant flavocoenzyme in body tissues. Production of FAD is controlled by product inhibition such that an excess of FAD inhibits its further production.
The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate as substrates. GTP is hydrolytically opened, converted into 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione by a sequence of deamination, side chain reduction and dephosphorylation. Condensation with 3,4-dihydroxy-2-butanone 4-phosphate obtained from ribulose 5-phosphate leads to 6,7-dimethyl-8-ribityllumazine. The final step in the biosynthesis of the vitamin involves the dismutation of 6,7-dimethyl-8-ribityllumazine catalyzed by riboflavin synthase. The mechanistically unusual reaction involves the transfer of a four-carbon fragment between two identical substrate molecules. The second product, 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, is recycled in the biosynthetic pathway by 6,7-dimethyl-8-ribityllumazine synthase. This article will review structures and reaction mechanisms of riboflavin synthases and related proteins up to 2007 and 122 references are cited.
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这种物质可以通过摄入被身体吸收。
The substance can be absorbed into the body by ingestion.
Riboflavin interrelates with other B vitamins, notably niacin, which requires riboflavin for its formation from tryptophan, and vitamin B6, which also requires riboflavin for a conversion to a conenzyme form. These interrelationships are not known to affect the requirement for riboflavin.
The rate and extent of absorption of riboflavin are reportedly affected by propantheline bromide. Prior administration of propantheline bromide delayed the rate of absorption of riboflavin but increased the total amount absorbed, presumably by increasing the residence time of riboflavin at GI absorption sites.
Riboflavin is readily absorbed from the upper GI tract; however, absorption of the drug involves active transport mechanisms and the extent of GI absorption is limited by the duration of contact of the drug with the specialized segment of mucosa where absorption occurs. Riboflavin 5-phosphate is rapidly and almost completely dephosphorylated in the GI lumen before absorption occurs. The extent of GI absorption of riboflavin is increased when the drug is administered with food and is decreased in patients with hepatitis, cirrhosis, biliary obstruction, or in those receiving probenecid.
Primary absorption of riboflavin occurs in the small intestine via a rapid, saturable transport system. A small amount is absorbed in the large intestine. The rate of absorption is proportional to intake, and it increases when riboflavin is ingested along with other foods and in the presence of bile salts. At low intake levels, most absorption of riboflavin occurs via an active or facilitated transport system. At higher levels of intake, riboflavin can be absorbed by passive diffusion.
In the plasma, a large portion of riboflavin associates with other proteins, mainly immunoglobulins, for transport. Pregnancy increases the level of carrier proteins available for riboflavin, which results in a higher rate of riboflavin uptake at the maternal surface of the placenta.
In the stomach, gastric acidification releases most of the coenzyme forms of riboflavin (flavin-adenine dinucleotide (FAD) and flavin mononucleotide (FMN)) from the protein. The noncovalently bound coenzymes are then hydrolyzed to riboflavin by nonspecific pyrophosphatases and phosphatases in the upper gut. Primary absorption of riboflavin occurs in the proximal small intestine via a rapid, saturable transport system. The rate of absorption is proportional to intake, and it increases when riboflavin is ingested along with other foods and in the presence of bile salts. A small amount of riboflavin circulates via the enterohepatic system. At low intake levels most absorption of riboflavin is via an active or facilitated transport system.
Synthesis and application of isotopically labeled flavin nucleotides
作者：Tatiana V. Mishanina、Amnon Kohen
DOI：10.1002/jlcr.3313
日期：2015.7
Flavin nucleotides, i.e. flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are utilized as prosthetic groups and/or substrates by a myriad of proteins, ranging from metabolic enzymes to light receptors. Isotopically labeled flavins have served as invaluable tools in probing the structure and function of these flavoproteins. Here we present an enzymatic synthesis of several radio- and stable-isotope labeled flavin nucleotides from commercially available labeled riboflavin and ATP. The synthetic procedure employs a bifunctional enzyme, Corynebacterium ammoniagenes FAD synthetase, that sequentially converts riboflavin to FMN and then to FAD. The final flavin product (FMN or FAD) is controlled by the concentration of ATP in the reaction. Utility of the synthesized labeled FAD cofactors is demonstrated in flavin-dependent thymidylate synthase. The described synthetic approach can be easily applied to the production of flavin nucleotide analogues from riboflavin precursors.
