Successful therapy with vitamin B6 and vitamin B2 of the carpal tunnel syndrome and need for determination of the RDAs for vitamins B6 and B2 for disease states.
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Carpal Tunnel Syndrome↗
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Inhibition of muscle glycogen phosphorylase b by vitamin B2 and its coenzyme forms.
Kinetic studies have demonstrated that vitamin B2 and its coenzyme forms FMN and FAD are potent inhibitors of glycogen phosphorylase b from rabbit skeletal muscle. The inhibition of the enzyme by flavins has a co-operative character (Hill coefficients exceed unity). Glycogen phosphorylase b bound to FMN or FAD does not reveal catalytic activity, whereas the enzyme bound to riboflavin retains about 16% of the initial catalytic activity.
Animals↗
The monocarboxylate transporter homolog Mch5p catalyzes riboflavin (vitamin B2) uptake in Saccharomyces cerevisiae.
Riboflavin is a water-soluble vitamin (vitamin B2) required for the production of the flavin cofactors FMN and FAD. Mammals are unable to synthesize riboflavin and need a dietary supply of the vitamin. Riboflavin transport proteins operating in the plasma membrane thus have an important role in the absorption of the vitamin. However, their sequences remained elusive, and not a single eukaryotic riboflavin transporter is known to date. Here we used a genetic approach to isolate MCH5, a Saccharomyces cerevisiae gene with homology to mammalian monocarboxylate transporters, and characterize the protein as a plasma membrane transporter for riboflavin. This conclusion is based on the suppression of riboflavin biosynthetic mutants (rib mutants) by overexpression of MCH5 and by synthetic growth defects caused by deletion of MCH5 in rib mutants. We also show that cellular processes in multiple compartments are affected by deletion of MCH5 and localize the protein to the plasma membrane. Transport experiments in S. cerevisiae and Schizosaccharomyces pombe cells demonstrate that Mch5p is a high affinity transporter (Km = 17 microM) with a pH optimum at pH 7.5. Riboflavin uptake is not inhibited by protonophores, does not require metabolic energy, and operates by a facilitated diffusion mechanism. The expression of MCH5 is regulated by the cellular riboflavin content. This indicates that S. cerevisiae has a mechanism to sense riboflavin and avert riboflavin deficiency by increasing the expression of the plasma membrane transporter MCH5. Moreover, the other members of the MCH gene family appear to have unrelated functions.
Biological Transport↗
Effect of different contents of proteins and vitamin B2 in the feed on the prevalence and infection intensity of Ascaridia galli in chickens.
A group of 10-day-old chickens was experimentally infected with a dose of 500 infective eggs of Ascaridia galli (Schrank, 1788) (Nematoda). Forty-nine days post infection the chickens were necropsied and the infection intensity and prevalence were determined. The group maintained on the feed containing 11% of protein showed higher infection intensity and prevalence compared to the chickens fed a diet containing 19% of protein. The addition of vitamin B2 to the feed containing 11% protein resulted in lower intensity and prevalence of the infection. In both series of experiments no effect of Zn-bacitracin or vitamin B2 on infection intensity or prevalence was observed for chickens fed feed containing 19% of protein.
Animal Feed↗
Protection by vitamin B2 against oxidant-mediated acute lung injury.
The effect of vitamin B2 (riboflavin) on oxidant-mediated acute lung injury has been examined in three different rat models. Pulmonary injury was induced by intravenous injection of cobra venom factor (CVF), by the intrapulmonary deposition of IgG immune complexes, or by hind limb ischemia-reperfusion. In each of the three models, injury was characterized by increases in vascular permeability (leakage of 125I-labeled bovine serum albumin), alveolar hemorrhage (extravasation of 51Cr-labeled rat erythrocytes), and neutrophil accumulation (myeloperoxidase activity). Intraperitoneal administration of riboflavin at a dose of 6 micromoles/kg body weight reduced vascular leakage by 56% in the CVF model, by 31% in the immune complex model, and by 53% in the lung injury model following ischemia-reperfusion of the hind limbs. Similar treatment reduced hemorrhage by 76%, 51%, and 70% in the three models of lung injury. In the CVF model, riboflavin was also shown to decrease products of lipid peroxidation (conjugated dienes) in lungs (by 45%) and in plasma (by 74%). Neutrophil accumulation in the lungs was not influenced by riboflavin administration in any of the three models. The studies demonstrate that riboflavin can mount a significant protection against oxidant-mediated inflammatory organ injury.
Animals↗
Vitamin B2 metabolism in the isolated perfused rat liver.
An investigation on vitamin B2 (V.B2) metabolism was undertaken, using perfused livers isolated from 1. normal rats, 2. riboflavin deficient rats, 3. choline deficient rats with fatty cirrhtic livers, and 4. alloxan diabetic rats, without the effect of extrahepatic factors. From the results, it was concluded that phosphorylation of V.B2 was performed in the liver, and was remarkably reduced in fatty cirrhosis. Moreover, in alloxan diabetic liver, the affected phosphorylation of V.B2 was improved by the infusion of insulin. The important role that liver performs on V.B2 metabolism, can be emphasized from these findings.
Animals↗
[Isolation of vitamin B2 auxotroph and preliminary genetic mapping in Salmonella typhimurium].
The first independent vitamin B2 auxotrophs of Salmonella typhimurium were obtained by using selective medium containing extraordinarily high concentration of B2 (300 micrograms/ml) after mutagenesis. Transduction analysis showed that 21 B2 auxotrophs could be divided into four groups, which were unlinked to each other. It means that at least 4 structural genes were involved in B2 biosynthetic pathway. Preliminary genetic mapping indicated that 2 genes located in 7'-22' and other 2 located in 22'-34' and 61.5'-69' region on the genetic map of S. typhimurium respectively.
Chromosome Mapping↗
Binding of vitamin B2 and its coenzyme forms by muscle glycogen phosphorylase b.
Binding of vitamin B2 and its coenzyme forms by glycogen phosphorylase b was studied by sedimentation velocity and sedimentation equilibrium methods. Microscopic dissociation constants for complexes of the enzyme with riboflavin, FMN and FAD were found to be 12.5, 6.8 and 18.1 microM, respectively (0.1 M KCl, pH 6.8, 20 degrees C). We revealed also that glucose 1-phosphate, glycogen and AMP decreased the affinity of the enzyme for FMN.
Adenosine Monophosphate↗
A spectrophotometric study of vitamin B2 and its coenzyme forms binding to muscle glycogen phosphorylase b.
The vitamin B2 and its coenzyme forms binding to glycogen phosphorylase b from rabbit skeletal muscle has been studied by the spectrophotometric method. The spectral properties of riboflavin, FMN and FAD bound to muscle glycogen phosphorylase b were found to be identical at the wavelengths of 300 to 500 nm. According to data on spectrophotometric titration of muscle glycogen phosphorylase b by FMN, each subunit of the enzyme contains one flavin-binding site.
Animals↗
Needle crystals of vitamin B2 induce polyploidy in Chinese hamster lung (CHL/IU) cells.
Induction of polyploidy by vitamin B2 (VB2) was investigated in cultured Chinese hamster lung (CHL/IU) cells. We report that VB2 in the form of needle crystals induces polyploidy via the formation of CHL/IU cells with more than one nucleus. The incidence of polyploid cells depended on the amount of needle crystals. No induction of polyploidy was observed when VB2 was used in solution. Electron-microscopic examination revealed that needle crystals adhered to the cell surface, and were enclosed by viscous cellular materials. These results indicate that needle crystals of VB2 have the ability to induce polyploidy in cultured CHL/IU cells, probably by physically fixing the shape of the cells and by this preventing normal mitosis.
Animals↗
[Effect of vitamins B2 and B6 on the functional properties of cholinoreceptors in molluscan neurons].
It is found that vitamins B2 and B6 modified the form of the acetylcholine response in identified Helix pomatia neurons. This effect is mainly conditioned by a delay in desensitization.
Acetylcholine↗
[The criteria for the vitamin B2 and B6 allowances of children suffering from celiac disease].
The relationship between the blood concentrations of vitamins B2 and B6 and excretion of their metabolites with the urine were studied in 34 children of both sexes aged 7 to 10 suffering from celiac disease. The study revealed that the criteria of adequate supply of these vitamins in the patients and healthy age-matched children differ. Riboflavin concentration of at least 90 ng/ml in red cells, at least 15 ng/ml in the blood plasma, and urinary excretion of at least 7 micrograms/h should be accepted as the criteria of this vitamin sufficiency in the organism. For vitamin B6 these values are 13 ng/ml pyridoxal phosphate in the blood plasma and urinary excretion of at least 47 micrograms/h of 4-pyridoxic acid.
Celiac Disease↗
Effect of a mixture of caffeine and nicotinamide on the solubility of vitamin (B2) in aqueous solution.
The effect of caffeine (CAF) and nicotinamide (NMD) on the solubility of a vitamin B2 derivative (FMN) has been evaluated for mixtures containing either a single hydrotrope (CAF or NMD) or the two hydrotropes simultaneously. A model for analysis of ternary systems, which takes into account all possible complexes between the molecules, has been developed and tested with experimental NMR data on the three-component mixture FMN-CAF-NMD. The results indicate that special attention should be given to the concentration of a hydrotropic agent used to enhance the solubility of a particular drug. A decrease in the efficacy of solubility of the vitamin on addition of large amounts of hydrotropic agent is expected in the two-component systems due to the increased proportion of self-association of the hydrotrope. It is found that a mixture of two hydrotropic agents leads to an increase in the solubility of the vitamin in three-component compared to the two-component system. Rather than using just one hydrotropic agent, it is proposed that a strategy for optimising the solubility of aromatic drugs is to use a mixture of hydrotropic agents.
Algorithms↗
Effect of vitamin B2 on somatic cell counts in milk of clinical Staphylococcus aureus mastitis.
Effects of intravenous injection of Vitamin B2 (VB2) on the nitroblue tetrazolium (NBT) reductivity of peripheral blood neutrophils and the somatic cell counts (SCC) in quarter milk of Staphylococcus aureus mastitis were investigated. The NBT reductivities of neutrophils were enhanced at 2 days after single injection of VB2 (5.0 and 2.5 mg/kg), and were also enhanced at 4 days after initial injection of continuous 3 days of VB2 (2.5 mg/kg). The SCC in quarter milk were significantly decreased at 3, 7 and 14 days after initial injection of continuous 3 days of VB2 (2.5 mg/kg), however, S. aureus in the infected quarter was not cured bacteriologically by VB2 injection.
Animals↗
Protective effect of Boldo and tea infusions on the visible light-mediated pro-oxidant effects of vitamin B2, riboflavin.
The effect of Boldo and black tea infusions on the pro-oxidant effects of vitamin B2, riboflavin (RF), when exposed to the action of visible light was studied. The amounts of antioxidants present in Boldo and tea infusions were evaluated by a procedure based on the bleaching of preformed 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cations and were expressed as 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid equivalent concentrations. The quenching rate constants of singlet oxygen (1O2; [kq]Boldo = 6.0 x 10(7) M(-1) s(-1) and [kq]Tea = 3.2 x 10(7) M(-1) s(-1)) and triplet RF (3RF; [3RFkq]Boldo = 10 x 10(8) M(-1) s(-1) and [3RFkq]TEA = 3.2 x 10(8) M(-1) s(-1)) with Boldo and tea were determined by flash photolysis. These data allow a quantitative interpretation of the results obtained. Our data suggest that most of the oxygen consumption observed in the photolysis of RF in the presence of tea and Boldo infusions is caused by 1O2 reactions. The oxygen consumption quantum yield is considerably smaller than the fraction of RF triplets trapped by the additives (AH) present in the infusion, indicating that their interaction with 3RF does not lead to chemical reactions or that the AH*+ radical ions initially formed participate in secondary processes that do not consume oxygen. Boldo and tea infusions have a significant protective effect when a system containing RF and tryptophan (Trp) is exposed to visible light, not only by quenching the 1O2 and interfering with the Type-I mechanism but also by repairing the damage to Trp molecules associated with the latter mechanism.
Chromans↗
Binding form of vitamin B2 in bovine milk: its concentration, distribution and binding linkage.
The contents of total, free, and bound vitamin B2 (B2) in bovine milk and their distribution in four separate milk fractions, including milk during the early lactation stage, were estimated. The total B2 content in whole mature milk was 179 +/- 25 micrograms/100 g (n = 16), and its distribution in the cream, whey, skim milk membrane, and casein fractions was 6, 67, 9, and 18%, respectively. The amount of flavins bound to protein in the total B2 was 13.6% in whole milk and rich in membrane fraction. The total B2 content (micrograms/100 g of milk) was higher in colostrum at 1-3 days (287 +/- 120) than in colostrum at 4-7 days (173 +/- 27), in transitional milk (182 +/- 33), and in mature milk (179 +/- 44). The bound flavin content decreased slightly as lactation progressed (20-30 micrograms/100 g), but the ratio of bound/total B2 did not vary (12-15%). Milk fat globule membrane (MFGM) contained 414 +/- 65 micrograms of B2/g of protein, most of it being bound to protein (92%). Market milks contained as much total B2 as raw whole milk, but the amount of bound form was only 2%. Guanidine HC1, urea, sodium dodecyl sulfate, pH at 3.0-3.5, delipidation, and boiling released most of the B2 bound to protein, suggesting that bound flavins bind to milk proteins by a hydrophobic linkage.
Animals↗
Vitamin B2 activity of 7,8-dimethyl-10-(2,3,4-trihydroxy-4-formylbutyl)isoalloxazine in Lactobacillus casei.
The microbial activities of vitamin B2-aldehyde and vitamin B2-acid, produced by Schizophyllum commune, a Basidiomycete, were studied. Lactobacillus casei ATCC No. 7469 was used as a test microorganism. B2-aldehyde exhibited a good response curve in the growth of L. casei. B2-acid had neither a stimulatory nor an inhibitory effect on the growth. When B2-aldehyde was incubated with the homogenate of L. casei, it was converted to riboflavin. The flavin formed from B2-aldehyde by the homogenate not only exhibited an equivalent response curve to authentic riboflavin in the growth of L. casei, but also showed the same Rf value as authentic riboflavin in any paper chromatogram, as far as tested. Hence, the microbial activity of B2-aldehyde for L. casei seems to be ascribable to riboflavin which is a reduction product of B2-aldehyde.
Dose-Response Relationship, Drug↗
Complexation of daunomycin with a DNA oligomer in the presence of an aromatic vitamin (B2) determined by NMR spectroscopy.
The effect of simultaneous binding of the anthracycline antibiotic Daunomycin (DAU) and the Vitamin B2 derivative, Flavin-mononucleotide (FMN), with the DNA oligomer, d(TGCA)2, in solution has been investigated quantitatively by 1I-NMR spectroscopy (500 MHz). The equilibrium reaction constants and the thermodynamical parameters (DeltaH, DeltaS) of the hetero-association FMN-DAU and complexation of FMN with d(TGCA)2 have been determined by analysis of the concentration and temperature dependences of chemical shifts of the aromatic protons in terms of a competitive binding model. A criterion for discrimination between hetero-association and DNA complexation has been developed and applied to the analysis of the simultaneous binding of the antibiotic and the vitamin with DNA. Under the conditions of the experiment, it is found that both the hetero-association of FMN with DAU and the complexation of FMN with DNA contribute approximately equally to the decrease of DAU binding with DNA oligomer. Such competitive complexation of aromatic vitamin and drug with DNA could affect the biological activity of such drugs.
Crystallography, X-Ray↗