Biotin formula

As mg/L of pantothenic acid. Formula also contains 150 Fg/L each of biotin and vitamin K. ... 

INDYK HE et al. (2000), Determination of biotin and folate in infant formula and milk by optical biosensor-based immunoassay , JAOCS, 83(5), 1141-8. 

Calculate the amount of a 10 mg/mL biotin succinimidyl ester solution (biotin-SE) needed to conjugate the desired quantity of antibody at the chosen biotin/ antibody molar ratio, according to the following formula ... 

The literature contains very little on methods for biotin determination in foods. Microbiological assays of biotin predominate in food work (19,180). Table 23 summarizes a recent HPLC method for the analysis of biotin in infant formula. 

Biotin and biotin analogs Infant formula Protein precipitation using concentrated hydrochloric acid neutralization with 6 M NaOH lipid extraction with n-hexane Precolumn Microsorb C18 (15 X 4.6 mm, 5 jam Rainin). Analytical Microsorb C18 (250 X 4.6 mm, 5 /zm Rainin). Isocratic 100 mM phosphate buffer, pH 7.0 + methanol (80 + 20, v/v). 0.4 ml/min. Postcolumn reaction system UV absorbance at 220 nm followed by streptavidin-fluorescein isothiocyanate (2.0 mg/L) knitted open tubular reaction system (10.0 m x 0.5-mm ID) at a flow rate External standardization. 184 Linear range = 0.08-1.00 fjM biotin. LoD = 0.02 /zM or 97 pg biotin at SNR = 3. Repeatability CV 3.5% for biotin in infant formula. 

Mixture of D-penicillamine (pen, Fig. 22) and copper(II) chloride forms a complex of the formula [Cu(I)8Cu(II)6pen12]5-. The Ri value of this complex at 300 MHz and 23°C is 0.586 mM 1 s-1 [178]. The carboxylate groups on the cluster have been shown to react with aziridines such as XAMA-7 (Fig. 23) which in turn can be reacted with biotin [179]. The copper clusters can then be attached to antibodies or other biotinylated proteins via an avidin linker molecule. 

Given its systematic name 5-[(3aS,4S,6a )-2-oxohexahydrothieno[3,4-d]-imidazol-4-yl]pentanoic acid, draw a structural formula with complete specification of the configuration for biotin (vitamin H). 

The structural formula (Figure 9-23) contains three asymmetric carbon atoms, and eight different stereoisomers are possible. Only the dextrorotatory D-biotin occurs in nature and has biological activity. Biotin occurs in some products in free form (vegetables, milk, and fruits) and in other products is bound to protein (organ meats, seeds, and yeast). Good sources of the vitamin are meat, liver, kidney, milk, egg yolk, yeast, vegetables, and mushrooms (Table 9-27). 

The bioassay was used to determine the bioavailability of zinc in milk-base and soy-base infant formulas (7). The results are shown in Figure 2 and Table 1. The low zinc basal diet contained (%) spray dried egg white powder, 20 com oil, 10 non-nutritive fibre, 3 starch, 25 biotin, 0.0004 vitamin mixture, 1 salt mixture, excluding zinc, 4 dextrose, 37. 

Figure 1. Structural formulas of the ethoxylated alcohol and phospholipid surfactants used in the affinity precipitation of avidin. Octaethyleneglycol mono-n-dodecylether (C12E8) was used as a solubilizing surfactant and dimyristoylphosphatidylethanolamine (DMPE) was used as the insoluble surfactant to which biotin was covalently attached. (The structural formula of the derivatized phospholipid and a discussion of the reaction and purification scheme have been previously described by Powers et (7)).

The UPLC-MS/MS method has also been developed for fast simultaneous separation and determination of 14 different water-soluble vitamins and vitamin-like compounds in infant formula (thiamine, riboflavin, pantothenic acid, nicotinic acid, nicotinamide, pyridoxine, pyridoxal, biotin, fohc acid, cyanocobalamin, ascorbic acid, L-camitine, choline, and taurine) [91], Methotrexate was also used as an internal standard for riboflavin, cyanocobalamin, biotin, and folic acid, while nicotinamide was used as an internal standard for the other compounds. 

The propionyl CoA carboxylation is another reaction in which the energy required to synthesize a car-bon-to-carbon bond is provided by ATP. Thus, the free energy of the pyrophosphate bond is transferred to CO2, which forms an N-carboxy bond with the biotin enzyme complex. Some of the molecular details of the propionyl carboxylation reaction are presented in Fig. 1-27. The isomerization of methylmalonyl CoA to succinyl CoA also involves vitamin B12. At first it was demonstrated that the activity of the isomerase was considerably decreased in the liver of vitamin B 12-deficient rats. Later the stimulating effect of 5,6-dimethylbenzimidazole carbamide coenzyme was demonstrated with partially purified preparations of the liver enzyme. The methylmalonate CoA-isomerase complex purified from sheep liver has been divided into two different protein fractions, one with isomerase and the other racemase activity. The isomerase acts on only one of the enantiomorphs of methylmalonyl CoA, but the absolute formula of the enantiomorph that serves as substrate for the isomerase is unknown. A racemase catalyzes the conversion of the alternate enantiomorph to the substrate of the isomerase. 

The relative binding response is interpolated from a calibration curve in order to compute concentration. As an inhibition assay, the response is inversely related to biotin concentration and exhibits a sigmoidal dose-response relationship that is typical of most ligand-binding assays. With respect to specificity, the routine compliance assay is targeted to the quantitation of free biotin only in nutritional dairy products, and therefore does not include biocytin (Indyk et al. 2000). However, in milk and supplemented infant formulas, the overwhelming majority of biotin is present in the free form. 

Human milk is the primary agent for infant nutriture and thereby guides the composition of manufactured infant formula and milk substitutes. The reported concentration of biotin in human milk is variable with lactation (and unfortunately between analytical methods), but is more than sufficient to supply the newborn infant with the RDI of 5-6pg/day, as evidenced by the absence of reported deficiency syndromes in breast-fed babies. Interestingly, most biotin in milk is present in a free form and therefore unbound with any macromolecules. As expected, when milk is separated into its fat and aqueous fractions, the water-soluble biotin is found predominantly in the skim-milk phase. Biotin has some lipophilidty and so a small percentage is carried into the cream as part of the fat-globule membrane. The total concentration of human milk is not large and somewhat similar to bovine milk. With respect to breast milk substitutes, it is necessary to ensure the biotin status remains comparable, thus international guidelines recommend 0.4-2.4pg/100 kJ of reconstituted or ready-to-feed infant formula. 

Infants fed on dairy-based formulae need additional biotin added to their food. 

Campos-Gimenez, E.C., Trisconi, M-J., Kilinc, T., and Andrieux, P., 2010. Optimization and validation of an LC-FLD method for biotin in infant formula, infant cereals, cocoa-malt beverages and clinical nutrition products. Journal of AOAC International. 93 1494—1502. 

Thompson, L.B., Schmitz, D.J., and Pan, S-J., 2006. Determination of biotin by high-performance liquid chromatography in infant formula, medical nutritional products and vitamin premixes. Journal of AO AC International. 89 1515-1518. 

An inadequate nutrition may cause biotin deficiency. Such deficiency would not appear if human alimentation was varied and regular. Biotin deficiency might occur with inadequate feeding formulas or with parenteral nutrition free of vitamin and mineral supplements. 

Concerning parenteral nutrition, the problem is the same but the existing formulas contain amino acids with adequate vitamin and mineral supplementation. Continuous consumption of raw eggs containing the protein avidin is well-known for causing biotin deficiency as the solid combination avidin/biotin is not absorbed. Nevertheless, such dietary intake is rather rare. Biotin deficiency can be considered as a public health problem in developing countries where severely malnourished children lack of multivitamins (Zempleni et al. 2008). 

Fujimoto, W., Inaoki, M., Fukui, T., Inoue, Y., and Kuhara, T., 2005. Biotin deficiency in an infant fed with amino acid formula. The Journal of Dermatology. 32 256-261. 

Teramura, K., Fujimoto, N., Tachibana, T., and Tanaka, T., 2010. Biotin deficiency in dizygotic twins due to amino acid formula nutrition. European Journal of Dermatology. 20 856 857. 

Watanabe, Y., Ohya, T., Ohira, T., Okada, J., Fukui, T., Watanabe, T., Inokuchi, T., Yoshino M., and Matsuishi, T., 2010. Secondary biotin deficiency observed in two Japanese infants due to chronic use of hypoallergic infant formula. Journal of Inherited Metabolic Disease. 33(Suppl 1) SI69 549-P. 

Biotin was found to have the empirical formula C10H16O3N2S. The electrometric titration showed that it was a simple monocarboxylic acid with a neutralization equivalent of 244. The hydrolysis yielded an optically active diamino-carboxyhc acid which had the composition C9H18O2N2S. It contained two primary amino groups as established by the Van Slyke method and could be reconverted to biotin by treatment with phosgenes. ... 

These reactions (i and z) are best explained by the presence of a urea ring. The sulfur was present in a thioether grouping. This was proved by the oxidation of biotin with hydrogen peroxides to the sulfone C10H16OSN2S. The empirical formula and the absence of ethylenic linkages indicated that... 

In 1942, do Vigneaud and associates, at Cornell, suggested the correct structural formula for biotin based on a study of its degradation products. 

MINERAL AND VITAMIN SUPPLEMENTS. There is considerable controversy among nutritionists and pediatricians regarding the amounts and types of nutrient supplements that are required by infants, since breast-fed infants have long been given little or no supplementation. Furthermore, the need for supplementation depends upon a variety of factors such as (1) status of the infant at birth, since preterm or low birth weight infants have higher nutritional requirements to attain the rates of growth and development of normal infants (2) type of milk or formula used (3) affliction of the infant with diarrhea, fever, infection, and/or other stresses and (4) age at which supplemental foods are introduced. It is noteworthy that even breast milk is low in iron, copper, fluoride, vitamins A, D, and E, and biotin, folacin, niacin, thiamin, and vitamin B-6. Furthermore, diluted evaporated milk is notably inferior to breast milk with respect to the contents of iron, zinc, vitamin A, vitamin E, and vitamin C. Therefore, the need for nutrient supplements should be evaluated by a health professional who is familiar with the diet and the overall health status of the infant. 

Biotin has been isolated as vitamin H from liver extracts (DuVigneaud and co-workers) and as one of the bios factors (yeast groivth factor) from egg yolk (Kogl and co-workers). It is a cyclic derivative of urea with an attached thiophane ring. The structural formula has been substantiated by synthesis. 

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