Biotin sulfone

Antagonists of biotin include desthiobiotin in some forms, ureylene phenyl, homobiotin, urelenecyclohexyl butync and valeric acid, norbiotin, avidin, lysolecithin. and biotin sulfone. Synergists indude vitamins B>. B6, B 2, folic acid, pantothenic add. somatotrophin (growth hormone), and testosterone. 

Figure 11.2. Biotin metabolites. Relative molecular masses (Mr) biotin, 244.3 biotin sulfoxide, 260.3 biotin sulfone, 276.3 bisnorbiotin, 212.3 tetranorbiotin, 180.3 and bisnorbiotin sulfoxide, 228.3.

Zempleni, J. McCormick, B. Mock, D.M. Identification of biotin sulfone, bisnorbiotin methyl ketone, and tetra-norbiotin-I-sulfoxide in human urine. Am. J. Clin. Nutr. 1997, 65, 508-511. 

About half of the absorbed biotin is excreted as the metabolites bisnorbiotin, occurring from fl-oxidation of the valeric acid side chain, and biotin sulfoxide, occurring from the oxidation of the sulfur in the heterocyclic ring. The circulating plasma and urinary excretion patterns show a ratio of 3 2 1 for biotin, bisnorbiotin, and biotin sulfoxide. Minor metabolites are bisnorbiotin methyl ketone and biotin sulfone. Careful balance studies in humans, where perhaps only 1 mg is the total body content, showed that urinary excretion of biotin often exceeded dietary intake, and that in aU cases, fecal excretion was as much as three to six times greater than dietary intake because of microfloral biosynthesis. 

In contrast to the reputation of lability of vitamins, biotin is very stable and can be autoclaved without being affected. This molecule can even resist autoclaving in concentrated sulfuric acid (4 M, 120°C, 2 h), conditions used to extract total biotin from biological samples (6). However, biotin can be easily oxidized into biotin sulfoxides and biotin sulfone (Fig. 2). This process, which is negligible... 

Figure 2 Structure of (-)biotin sulfoxide, (+)biotin sulfoxide, and biotin sulfone.

Mock has described a very sensitive method (the limit of detection is around 5 fmol) for the detection of biotin and its metabolites, involving C18 reversed-phase HPLC separation followed by detection using an avidin-horseradish peroxidase conjugate (92). The principle of this method has already been discussed. This methodology has allowed the identification and quantification of biotin, bisnorbi-otin, biotin sulfoxides, and biotin sulfone in human and animal serum and urine. Furthermore, new biotin metabolites (tetranorbiotin sulfoxide and bisnorbiotin methyl ketone) were detected in human urine (114). This technique should potentiate more accurate studies on human biotin metabolism (see, e.g., 115). 

Figure 17 HPLC separation of BAP esters (a) and Mmc esters (b) of biotin and some analogs. Peaks (1) (—) biotin sulfoxide (2) ( + ) biotin sulfoxide (3) biotin sulfone (4) biotin (5) dethiobiotin. Conditions two 330 X 4 mm C18 bonded columns (Waters) directly connected were used gradient THF-water from 30 70 to 60 40 flow rate 1 mL/ min. (From Ref. 109.)...

Janecke and Voege (119) attempted to determine biotin and its oxidation products in commercial multivitamin preparations using the silylation technique. However, the separation of biotin, biotin sulfone, and sulfoxides from a multivitamin mixture was not complete, and the two isomeric sulfoxides could not be separated. 

Biotin is found in a range of foods, but the concentration in most of them is usually low (Table 5.8). It is partly present as a free compound (milk, fruits and vegetables) and partly bound to proteins (animal tissues, plant seeds and yeast). Yeast autolysates, for example, contain free biotin and its precursors and analogues. These biotin vitamers, mainly dethiobiotin (5-85), biotin sulfone (5-90) and biocytin (5-87), are degradation products of enzymes containing biotin. 

Biotin is stable when heated, in the Hght, in neutral and strongly acidic solutions. It is unstable in alkaline media. It is easily oxidised by hydrogen peroxide and other oxidants to a mixture of isomeric (-1-)- and (-)-sulfoxides (5-88 and 5-89), eventually to biotin sulfone (5-90). Sulfoxides also form as metaboHc products of microorganisms. They are ftiUy available, whereas sulfone is unavailable as a vitamin. Nitrogen of a ureido ring maybe nitrosated to nitrosobiotin (5-91) in the presence of nitrites or nitrogen oxides. 

Additional studies have shown that [ Cjbiotin injected i.p. into rats as the avidin complex was excreted much more slowly than the free vitamin. Nevertheless, the biotin-avidin complex was dissociated in vivo and the released biotin excreted and metabolized to sulfoxides and bisnorbiotin. That liver has the capacity to cause such dissociation and metabolism was demonstrated. The rate and extent of excretion of bisnorbiotin is essentially the same as for biotin. The more water-soluble tetranorbiotin, both d- and J-sulfoxides of biotin, and biotin sulfone were excreted even more rapidly. 

Growth-inhibitions by compounds structurally related to biotin have been observed. These are different in kind from the action of the antibiotin factor, where an inactive protein complex is formed. These structurally related anti-metabolites include biotin sulfone and desthiobiotin, their activities being related to the nutritional requirements of the organ-... 

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