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PubMed1997

Serum concentrations of bisnorbiotin and biotin sulfoxide increase during both acute and chronic biotin supplementation.

In addition to the pharmacokinetic interest, serum concentrations of biotin and biotin metabolites are important because biotin in serum might interfere with assays that use avidin-biotin detection systems. With acute and chronic oral administration of biotin the serum concentration of biotin increases. Because of limited specificity of bioassays or avidin-binding assays used in previous studies, the proportion of the increase attributable to biotin metabolites (if any) remains unknown. To address these questions 15 adults consumed 1,200 microg biotin daily for 14 days. Blood samples were obtained before biotin ingestion and at 3 hours after biotin ingestion on the first day ("acute supplementation") and the fourteenth day ("chronic supplementation"). Biotin, bisnorbiotin, and biotin sulfoxide were measured with a chemically specific high-pressure liquid chromatography/avidin-binding assay. Serum concentrations of biotin, bisnorbiotin, and biotin sulfoxide increased approximately fiftyfold with acute supplementation of biotin; each increased further with chronic supplementation. With acute supplementation the proportion of the total attributable to metabolites did not decrease significantly, suggesting that pathways for biotin catabolism are not easily saturated. With chronic supplementation the proportion of the total attributable to metabolites did not increase significantly, suggesting that biotin catabolism was not substantially induced. We conclude that on a mole basis the contribution of biotin metabolites is important, and we provide an estimate of the biotin and biotin metabolite concentration that might be encountered in individuals who self-select large biotin supplements.

Adult↗
PubMed1999

Advanced analysis of biotin metabolites in body fluids allows a more accurate measurement of biotin bioavailability and metabolism in humans.

In previous studies, the bioavailability of biotin in humans was estimated from the recovery of biotin in urine; urinary biotin was measured by microbial growth assays or assays of avidin-binding activity. These assays underestimate concentrations of biotin metabolites, which originate from beta-oxidation, sulfur oxidation or a combination. We have developed an HPLC/avidin-binding assay that is specific for biotin and its metabolites. With the use of the HPLC/avidin-binding assay, TLC and derivatization with p-dimethylaminocinnamaldehyde, we have identified and quantitated biotin and metabolites in urine from six healthy adults. Of that total, biotin accounted for 32+/-12%, bisnorbiotin for 52+/-15%, bisnorbiotin methyl ketone for 7.9+/-5.8%, biotin-d,l-sulfoxide for 4.0+/-3.2% and biotin sulfone for 3.6+/-1.9%. After intravenous administration of 18.4 micromol of biotin, the urinary excretion of biotin metabolites increased 21-130 times above baseline values. Because the biliary excretion of biotin is quantitatively minor (1.9+/-0.2% of an intravenous [14C]biotin dose in rats), intravenously administered biotin is not exposed to intestinal microorganisms. Thus we conclude that biotin metabolites in human urine originate from biotin catabolism in human tissues rather than biotin catabolism by intestinal microorganisms. With the use of the HPLC/avidin-binding assay, we estimated the bioavailability of biotin in adults from the urinary excretion of biotin and metabolites after ingestion of 2.1, 8.2 and 81.9 micromol of biotin. These data provide evidence that biotin is nearly completely absorbed.

Animals↗
PubMed2002

Biotin supply affects expression of biotin transporters, biotinylation of carboxylases and metabolism of interleukin-2 in Jurkat cells.

Biotin supply may affect transcription of genes and biotinylation of proteins in cells. In this study, Jurkat cells were used to model effects of biotin supply on biotin homeostasis and interleukin-2 metabolism in immune cells. Cells were cultured in media containing deficient (25 pmol/L), physiologic (250 pmol/L), or pharmacologic concentrations (10,000 pmol/L) of biotin for 4 wk. Activities of the biotin-dependent enzyme propionyl-CoA carboxylase paralleled the biotin concentrations in media [pmol bicarbonate fixed/(min x 10(6) cells)]: 1.9 +/- 0.7 (25 pmol/L biotin) vs. 19 +/- 1.2 (250 pmol/L biotin) vs. 40 +/- 2.0 (10,000 pmol/L biotin). Cells responded to biotin deficiency with increased expression of biotin transporter genes. Biotin-deficient cells maintained normal biotinylation of histones but contained reduced levels of biotinylated carboxylases, suggesting compartmentalization of intracellular biotin distribution. Rates of cell proliferation and activities of the apoptotic enzyme caspase-3 were similar among treatment groups, suggesting that net proliferation was not affected by biotin status. Net secretion of interleukin-2 by Jurkat cells was inversely associated with the biotin concentration in media [kU/(L x 24 h x 10(6) cells)]: 21 +/- 1.8 (25 pmol/L biotin) vs. 15 +/- 5.4 (250 pmol/L biotin) vs. 6.1 +/- 1.8 (10,000 pmol/L biotin), suggesting increased secretion or decreased internalization of interleukin-2 by biotin-deficient cells. This study provides evidence that biotin supply affects biotinylation of proteins, gene expression and metabolism of interleukin-2 in Jurkat cells. The physiological significance of effects of biotin status on metabolism of interleukin-2 remains to be elaborated.

Biotin↗
PubMedDate not supplied

Biotin reagents for antibody pretargeting. 4. Selection of biotin conjugates for in vivo application based on their dissociation rate from avidin and streptavidin.

An investigation was conducted to determine the affect of structural variation of biotin conjugates on their dissociation rates from Av and SAv. This information was sought to help identify optimal biotin derivatives for in vivo applications. Fifteen biotin derivatives were conjugated with a cyanocobalamin (CN-Cbl) derivative for evaluation of their "relative" dissociation rates by size exclusion HPLC analysis. Two biotin-CN-Cbl conjugates, one containing unaltered biotin and the other containing iminobiotin, were prepared as reference compounds for comparison purposes. The first structural variations studied involved modification of the biotinamide bond with a N-methyl moiety (i.e., sarcosine conjugate), lengthening the valeric acid side chain by a methylene unit (i.e., homobiotin), and replacing the biotinamide bond with thiourea bonds in two conjugates. The rate of dissociation of the biotin-CN-Cbl derivative from Av and SAv was significantly increased for biotin derivatives containing those structural features. Nine additional biotin conjugates were obtained by coupling amino acids or functional group protected amino acids to the biotin moiety. In the conjugates, the biotin moiety and biotinamide bond were not altered, but substituents of various sizes were introduced alpha to the biotinamide bond. The results obtained from HPLC analyses indicated that the rate of dissociation from Av or SAv was not affected by small substituents alpha to the biotinamide (e.g., methyl, hydroxymethyl, and carboxylate groups), but was significantly increased when larger functional groups were present. On the basis of the results obtained, it appears that biotin conjugates which retain an unmodified biotin moiety and have a linker molecule conjugated to it that has a small functional group (e.g., hydroxymethylene or carboxylate) alpha to the biotinamide bond are excellent candidates for in vivo applications. These structural features are obtained in the biotin amino acid conjugates: biotin-serine, biotin-aspartate, biotin-lysine, and biotin-cysteine. Importantly, these biotin derivatives can be readily conjugated with other molecules for specific in vivo applications. In our studies, these derivatives will be used in the design of new biotin conjugates to carry radionuclides for cancer therapy using the pretargeting approach.

Antibodies↗
PubMed2006

Biotin sensing in Saccharomyces cerevisiae is mediated by a conserved DNA element and requires the activity of biotin-protein ligase.

Biotin is a water-soluble vitamin that functions as a prosthetic group in carboxylation reactions. In addition to its role as a cofactor, biotin has multiple roles in gene regulation. We analyzed biotin effects on gene expression in the yeast Saccharomyces cerevisiae and demonstrated by microarray, Northern, and Western analyses that all yeast genes encoding proteins involved in biotin metabolism are up-regulated following biotin depletion. Many of these genes contain a palindromic promoter element that is necessary and sufficient for mediating the biotin response and functions as an upstream-activating sequence. Mutants lacking the plasma membrane biotin transporter Vht1p display constitutively high expression levels of biotin-responsive genes. However, they react normally to biotin precursors that do not require Vht1p for uptake. The biotin-like effect of precursors with regard to gene expression requires their intracellular conversion to biotin. This demonstrates that Vht1p does not act as a sensor for biotin and that intracellular biotin is crucial for gene expression. Mutants with defects in biotin-protein ligase, similar to vht1delta mutants, also display aberrantly high expression of biotin-responsive genes. Like vht1delta cells, they have reduced levels of protein biotinylation, but unlike vht1delta mutants, they possess normal levels of free intracellular biotin. This indicates that free intracellular biotin is irrelevant for gene regulation and identifies biotin-protein ligase as an important element of the biotin-sensing pathway in yeast.

Base Sequence↗
PubMed1996

The metabolite profile of radioisotope-labeled biotin in rats indicates that rat biotin metabolism is similar to that in humans.

The egg white-fed rat is the most commonly used animal model of human biotin deficiency. We sought to determine whether the urinary excretion rates of biotin and biotin metabolites in rats are similar to those reported in humans. D-(Carbonyl-14C)biotin was injected intraperitoneally at physiologic doses in 6- to 10-wk-old rats; HPLC and radiometric flow detection were used to specifically identify and quantify biotin and metabolites in urine. Substantial amounts of bisnorbiotin and biotin sulfoxide, the two principal human metabolites, were detected. The excretion rates of biotin and metabolites were strikingly dependent on the dose of biotin. When the dose of [14C]biotin was 30% of the daily dietary intake (a physiologic dose), 50% of the administered 14C was excreted within 24 h; more than half of the excretion was the unchanged vitamin. After d 1, [14C]bisnorbiotin was the major form excreted. For the cumulative 5-d excretion, [14C]biotin accounted for 46 +/- 9%, [14C]bisnorbiotin accounted for 47 +/- 11 %, and [14C]biotin sulfoxide accounted for 8 +/- 4% of the total of biotin, bisnorbiotin, and biotin sulfoxide recovered radioactivity (mean +/- 1 SD, n = 6). These proportions are similar to those reported in humans: biotin = 52 +/- 12%, bisnorbiotin = 35 +/- 9%, and biotin sulfoxide = 13 +/- 4% of total biotin plus metabolites (mean +/- 1 SD, n = 10). Thus, these studies confirm the earlier identification of bisnorbiotin and biotin sulfoxide as the two principal biotin metabolites and provide evidence that the rat is an appropriate model for human biotin metabolism.

Animals↗
PubMed2002

Biotin dependency due to a defect in biotin transport.

We describe a 3-year-old boy with biotin dependency not caused by biotinidase, holocarboxylase synthetase, or nutritional biotin deficiency. We sought to define the mechanism of his biotin dependency. The child became acutely encephalopathic at age 18 months. Urinary organic acids indicated deficiency of several biotin-dependent carboxylases. Symptoms improved rapidly following biotin supplementation. Serum biotinidase activity and Biotinidase gene sequence were normal. Activities of biotin-dependent carboxylases in PBMCs and cultured skin fibroblasts were normal, excluding biotin holocarboxylase synthetase deficiency. Despite extracellular biotin sufficiency, biotin withdrawal caused recurrent abnormal organic aciduria, indicating intracellular biotin deficiency. Biotin uptake rates into fresh PBMCs from the child and into his PBMCs transformed with Epstein Barr virus were about 10% of normal fresh and transformed control cells, respectively. For fresh and transformed PBMCs from his parents, biotin uptake rates were consistent with heterozygosity for an autosomal recessive genetic defect. Increased biotin breakdown was ruled out, as were artifacts of biotin supplementation and generalized defects in membrane permeability for biotin. These results provide evidence for a novel genetic defect in biotin transport. This child is the first known with this defect, which should now be included in the identified causes of biotin dependency.

Amidohydrolases↗
PubMed1965

CONVERSION OF D-BIOTIN TO BIOTIN VITAMERS BY LACTOBACILLUS ARABINOSUS.

Birnbaum, Jerome (University of Cincinnati College of Medicine, Cincinnati, Ohio), and Herman C. Lichstein. Conversion of d-biotin to biotin vitamers by Lactobacillus arabinosus. J. Bacteriol. 89:1035-1040. 1965.-Saccharomyces cerevisiae utilizes d-biotin, biotin sulfoxide, and several vitamers of biotin, whereas Lactobacillus arabinosus responds to biotin and biotin sulfoxide of the naturally occurring forms of the vitamin. The use of these organisms for differential assay permitted investigation into possible conversion of d-biotin to vitamers of biotin by cells of L. arabinosus. Cells were grown in modified Wright-Skeggs medium containing several levels of biotin. No differences were detected between the assays for free intracellular or bound biotin up to 48 hr of growth. However, at 15 to 16 hr, in media containing an excess of biotin, the lactobacillus assay value for menstruum biotin dropped markedly, whereas the yeast assay showed no change. This suggested that biotin was converted to vitamers not active for L. arabinosus. The biotin-converting system appears to have characteristics of an enzyme system, i.e., a temperature optimum at 37 C, a broad pH optimum of 4.3 to 6.5, and requirements for Mg and Mn ions. Experiments suggest that increasing hydrogen ion concentration is a major physiological mechanism controlling the formation of this system. The vitamers were separated chromatographically and were found to have R(F) values of 0.44 and 0.94, and are combinable and uncombinable with avidin, respectively. The physiological role of biotin conversion is discussed in relation to control of cell populations in cultures of L. arabinosus.

Biological Assay↗
PubMedDate not supplied

Biotin reagents for antibody pretargeting. Synthesis, radioiodination, and in vitro evaluation of water soluble, biotinidase resistant biotin derivatives.

As part of our development of antibody pretargeting for cancer therapy, an investigation has been conducted to examine the stability of water solubilized, radioiodinated biotin derivatives toward biotinidase degradation in mouse and human serum. Eight new biotin derivatives were synthesized to conduct the study. The biotin derivatives synthesized contained (1) the biotin moiety, (2) a water solubilizing linker moiety, (3) p-iodobenzoate or p-tri-n-butylstannylbenzoate moieties, and (4) in some of the compounds, N-methyl or alpha-methyl containing moieties were added to block biotinidase activity. The linker moiety, 4,7,10-trioxa-1,13-tridecanediamine, 5, was included in the biotin derivatives to improve their water solubility, and it also functioned as a 17 A spacer between the biotin and the benzoyl moieties. Four of the new biotin derivatives (12, 14, 22, and 23) contained a p-tri-n-butylstannylbenzoyl moiety as precursors which could be radioiodinated in the last synthetic step. The other four biotin derivatives (13, 15, 24, and 25) contained p-iodobenzoyl moieties and were used as HPLC reference standards. Initial studies involved radioiodination of 12 to yield [125I]13. Radioiodinated 13, which did not contain a moiety for blocking biotinidase activity, was found to be rapidly degraded in both mouse and human serum at 37 degrees C. Derivatives which were designed to be stable to biotinidase incorporated N-methyl and alpha-methyl moieties adjacent to the biotin carboxylate group. In one set of biotin derivatives (14 and 15), the N-methyl moiety was obtained by incorporating N,N-dimethyl-4,7,10-trioxa-1,13-tridecanediamine, 9, as a linker in the place of 5. In the second set of biotin derivatives (22 and 24), the N-methyl moiety was introduced by incorporating a sarcosine (N-methylglycine) moiety between biotin and 5. The radioiodinated N-methyl containing biotin derivatives [125I]15 and [125I]24 were found to be very stable to biotinidase degradation. An alpha-methyl group was obtained in a pair of biotin derivatives (23 and 25) by incorporating a 3-aminobutyric acid moiety between biotin and 5. The radioiodinated alpha-methyl containing derivative, [125I]25, was found to have an intermediate stability with regards to biotinidase degradation.

Amidohydrolases↗
PubMed1986

Effect of biotin supplementation of a barley-wheat diet on restoration of healthy feet, legs and skin of biotin deficient sows.

Sixteen sows with induced biotin deficiency were divided into groups of four and fed an egg-white-free barley-wheat based diet without added biotin (control) or supplemented with one of three levels of synthetic d-biotin (100, 200 or 400 micrograms kg-1) for two parities in order to determine the optimal level required to reverse symptoms of the deficiency and to evaluate the relationship among dietary biotin levels, stage of recovery and serum biotin concentrations. Biotin supplementation significantly reduced (P less than 0.05) the incidence of lesions (on the foot pads, above the dew claws and on the skin) and also dry skin, but had no effect (P greater than 0.05) on hoof cracks, hair score or hair density. Time after supplementation had significant effects on reversal of most biotin deficiency symptoms. Interactions between biotin supplementation and time after supplementation suggested that these symptoms were reversed more quickly when higher levels of biotin were fed. Serum biotin concentrations of biotin-supplemented sows were increased with time and exceeded 600 ng litre-1 after 0.5, 1.0 and 1.5 months following biotin supplementation of the basal diet with 400, 200 and 100 micrograms kg-1. In contrast, serum biotin concentrations of the control sows remained low and peaked at 411 ng litre-1 after 2.5 months. The data suggested that supplementation of a barley-wheat diet to provide 147 to 217 micrograms available biotin kg-1 might be adequate to restore healthy feet, legs and skin and concurrently maintain high serum biotin concentrations.

Animal Feed↗
PubMed1993

A comparison of the binding of biotin and biotinylated macromolecular ligands to an anti-biotin monoclonal antibody and to streptavidin.

A competitive enzyme immunoassay was used to study the binding of biotinylated macromolecular ligands and d-biotin to an anti-biotin monoclonal antibody and to streptavidin. Solid phase BSA-c-biotin competed with biotin or biotinylated macromolecular ligands in solution for receptor binding. The concentration of d-biotin required to inhibit streptavidin binding to solid phase BSA-c-biotin by 50% was 11.5 pM. This streptavidin-biotin interaction was taken as having an affinity/avidity index of 100 and all other receptor-ligand interactions were calculated relative to this. The avidity indices calculated for streptavidin interactions with BSA-c-biotin and IgG-biotin were 17.6 and 6.6 respectively, whereas for anti-biotin the values for these ligands were 20.5 and 19.9 respectively. The interaction of anti-biotin with d-biotin had an affinity index of 0.001. Although streptavidin has the greatest binding affinity for d-biotin, its avidity for biotinylated ligands was considerably lower and comparable to that observed for anti-biotin-biotinylated macromolecule interactions.

Animals↗
PubMed2005

Biotin availability regulates expression of the sodium-dependent multivitamin transporter and the rate of biotin uptake in HepG2 cells.

In human cells, biotin is essential to maintain metabolic homeostasis and as regulator of gene expression. The enzyme holocarboxylase synthetase (HCS) transforms biotin into its active form 5'-biotinyl-AMP and this compound is used to biotinylate five biotin-dependent carboxylases or to activate a soluble guanylate cyclase (sGC) and a cGMP-dependent protein kinase (PKG). The HCS-sGC-PKG pathway is responsible for maintaining the mRNA levels of enzymes involved in biotin utilization including HCS, carboxylases, and a biotin carrier known as sodium-dependent multivitamin transporter (SMVT). To understand the role of SMVT in the control of biotin utilization, we have studied the effect of biotin availability on SMVT protein and mRNA expression levels in HepG2 cells by Western blot analysis and rtPCR, respectively; and their functional impact on the rate of [3H]biotin uptake in human cells. Our results showed that human HepG2 cells grown in a biotin-deficient medium have a lower rate of biotin uptake than normal cells. The impairment in biotin uptake is associated with a reduction in the amount of both SMVT protein mass and mRNA levels. Transfection of HepG2 cells with a vector containing a luciferase reporter gene under the control of the rat SMVT promoter demonstrated that its transcriptional activity is regulated by biotin availability through activation of the HCS-sGC-PKG pathway. Our results support the proposed role of SMVT in the altruistic regulation of biotin utilization in liver cells that has been associated with sparing biotin depletion of the brain.

Animals↗
PubMedDate not supplied

Biotin reagents in antibody pretargeting. 6. Synthesis and in vivo evaluation of astatinated and radioiodinated aryl- and nido-carboranyl-biotin derivatives.

An investigation has been conducted to prepare and evaluate several radiohalogenated biotin derivatives as part of our studies to develop reagents for carrying (211)At in cancer pretargeting protocols. The primary goal of the investigation was to determine the in vivo stability and distribution properties of astatinated biotin derivatives. In addition to astatination, the biotin derivatives were radioiodinated for in vitro and in vivo comparison. Biodistributions were conducted in athymic mice, with sacrifice times of 1, 4, and 24 h to correspond to 9%, 32%, and 90% of (211)At decay (t(1/2) = 7.21 h). In the investigation, two biotin derivatives, 1a and 2a, were synthesized which had structures that contain a biotin moiety, a biotinidase-blocking moiety, an ether linker moiety, and an aryl stannane moiety for radiohalogenation. Biotin derivatives 1a and 2a were radiolabeled with (125/131)I to give [(125)/(131)I]1b or [(125)I]2b and with (211)At to give [(211)At]1c or [(211)At]2c. In vivo studies demonstrated that co-injected [(125)I]2b and [(131)I]1b had very similar tissue distributions in athymic mice. Co-injection of [(211)At]2c and [(125)I]2b provided data that indicated that rapid deastatination occurred in vivo. A second set of biotin derivatives, 3a, 4a, and 5a, were synthesized which had structures that contain a biotin moiety, a biotinidase-blocking moiety, and an anionic nido-carborane moiety for radiohalogenation. The biotin derivatives 4a and 5a contained an aryl moiety not present in 3a, and 5a had a trialkylamine functionality not present in 3a or 4a. Biotin derivative 3a was radioiodinated, but was not further investigated. Biotin derivatives 4a and 5a were radiolabeled with (211)At and (125)I to produce [(125)I]4b/[(211)At]4c and [(125)I]5b/[(211)At]5c. Comparison of [(125)I]4b and (separately) [(125)I]5b with [(131)I]1b showed that the nido-carborane containing biotin derivatives were retained in blood and tissue more than the aryl iodide derivative. In vivo evaluations of [(211)At]4c/[(125)I]4b and (separately) [(211)At]5c/[(125)I]5b indicated that some deastatination occurred in these compounds, but it was much less than observed for the aryl derivative [(211)At]2c. While the nido-carborane containing biotin derivatives provide a significant improvement in astatine stability over biotin derivatives previously studied, additional derivatives need to be prepared and studied to further improve the in vivo stability and blood/tissue clearance of these compounds.

Animals↗
PubMed1989

Biotin studies in pigs. 5. The post-ileal absorption of biotin.

Six pigs were given a biotin-deficient diet (10 micrograms biotin/kg) for 14 weeks. The pigs were given the same diet for a further 42 d with one of three biotin treatments: no supplement, 400 micrograms biotin/d given orally, 400 micrograms biotin/d infused into the caecum. The concentrations of biotin in the liver, kidney and heart, at the conclusion of 42 d were greater in the pigs given the oral biotin supplement than in the unsupplemented pigs. The values for the pigs given the caecal infusion of biotin were intermediate. The excretion of biotin in faeces was increased from 35 to 101 micrograms/d by the caecal biotin infusion, and the urinary excretion was increased from 35 to 83 micrograms/d. The oral dose of biotin increased urinary biotin excretion from 35 to 345 micrograms/d, but there was no change in faecal biotin excretion. Two pigs were fitted with ileal cannulas and catheters in the vena cava. The pigs were given a dose of [14C] biotin either into the caecum, when the ileum was occluded by a bladder catheter, or orally. [14C] biotin was measured in the urine and plasma and showed that post-ileal biotin absorption was 8% as efficient as the absorption of biotin after oral dosing.

Animals↗
PubMed2003

Pharmacological biotin supplementation maintains biotin status and function in rats administered dietary carbamazepine.

Biotin status and function are decreased during oral carbamazepine (CBZ) administration in both humans and rats, but it is not known whether biotin supplementation can prevent these decreases. To test the effectiveness of pharmacologic biotin supplementation during CBZ administration, 55 rats were randomly divided into 4 groups (0.06 mg biotin/kg diet +/- 3.75 g CBZ/kg diet and 6.0 mg biotin/kg diet +/- 3.75 g CBZ/kg diet). CBZ and biotin-supplemented diets began on d 5 and 26, respectively, and continued through d 68. Rats (n = 5/group) were killed on d 5, 26, 47 or 68. CBZ reduced serum and liver free biotin (P < 0.05), whereas biotin supplementation during CBZ administration maintained biotin status. CBZ also decreased specific activities and abundance of biotinylated pyruvate and acetyl CoA carboxylases (PC and ACC, P < 0.05) in brain and liver, whereas biotin supplementation prevented these decreases for ACC. Specific activity of PC was maintained upon biotin supplementation, but the abundance of biotinylated PC remained significantly decreased. Brain and serum lactate were elevated after 68 d of CBZ treatment and were reduced to control lactate concentrations upon biotin supplementation (P < 0.05). Conversion of lactate to pyruvate and simultaneous generation of NADH during biotin supplementation could explain how increases in PC activity occur without changes in the abundance of biotinylated PC because we found NADH to be an activator of PC activity in vitro. These results support the use of biotin supplementation as a concurrent strategy during CBZ administration to help maintain biotin status, function of biotin-dependent enzymes and decrease CBZ-induced lactate accumulation.

Animals↗
PubMed1978

Uptake of extracellular biotin by Escherichia coli biotin prototrophs.

Uptake of exogenous biotin by two Escherichia coli biotin prototroph strains, K-12 and Crookes, appeared to involve incorporation at a fixed number of binding sites located at the cell membrane. Incorporation was characterized as a binding process specific for biotin, not requiring energy, and stimulated by acidic pH. Constant saturation quantities of exogenous biotin were incorporated by these cells, and the amounts, which were titrated, depended on whether the cells were resting or dividing. Resting cells incorporated exogenous biotin amounting to 2% of their total intracellular biotin content. Fifty percent of the exogenous biotin was incorporated into their free biotin fraction, and 50% was incorporated into their bound biotin fraction. On the other hand, dividing cells incorporated exogenous biotin into all of their intracellular sites, 88% going into the intracellular-bound biotin fraction, and 12% going into the free biotin fraction. Calculations suggested that each cell contained approximately 3,000 binding sites for biotin. It was postulated that biotin incorporation sites might have been components of acetyl coenzyme A carboxylase located at or near the membrane.

Avidin↗
PubMed2002

Acute glucocorticoid treatment increases urinary biotin excretion and serum biotin.

Previous studies have demonstrated that glucocorticoids alter biotin metabolism. To extend these studies, the effect of dexamethasone on biotin pools was analyzed in rats consuming a purified diet containing a more physiological level of dietary biotin intake (0.06 mg/kg). Acute (5 h) dexamethasone administration (0.5 mg/kg) elicited elevated urinary glucose output as well as elevated urinary biotin excretion and serum biotin. Renal and hepatic free biotin was also significantly elevated by acute dexamethasone administration. Chow-fed rats treated with an acute administration of dexamethasone demonstrated significantly elevated urinary glucose excretion, urinary biotin excretion, and serum biotin, but no change in tissue associated biotin was detected. Chronic administration of dexamethasone (0.5 mg/kg ip) over 4 days significantly elevated urinary glucose excretion 42% but had no effect on urinary biotin excretion, serum biotin, or hepatic- or renal-associated free biotin. These results demonstrate the existence of potentially novel regulatory pathways for total biotin pools and the possibility that experimental models with high initial biotin status may mask potentially important regulatory mechanisms.

Animals↗
PubMed1997

Effect of endogenous biotin on the applications of streptavidin and biotin in mice.

The use of streptavidin-conjugated antibody to pretarget tumors in animals and patients, prior to administration of radiolabeled biotin, has provided encouraging results, in part because of the high affinity of biotin for streptavidin and the rapid whole-body clearance of biotin. However, binding of endogenous biotin to streptavidin may interfere with the clinical potential of this approach. This report evaluates the effect of endogenous biotin on an antibody-streptavidin conjugate in a mouse tumor model. Tumored nude mice were depleted of endogenous biotin by sequential intraperitoneal injections of streptavidin. The assay of serum biotin levels indicated less than 0.5 ng of biotin per mL of serum in treated mice versus 4 ng per mL in untreated animals. Flow cytometric analysis was used on single-cell suspensions of tumor from animals receiving streptavidin-conjugated IgG to detect the presence of the antibody on the cell membrane (with fluoroisothiocyanate-conjugated goat anti-mouse antibody), and to detect biotin binding sites on streptavidin (with biotin-phycoerythrin). Both treated and untreated mice demonstrated the presence of antibody on tumor cells through 48 h postadministration, but only in treated animals were biotin binding sites observed. These results in the mouse model suggest that the small concentration of streptavidin delivered to a tumor via a specific antibody may be saturated with endogenous biotin and therefore not able to be targeted subsequently with radiolabeled biotin.

Animals↗