Bisnorbiotin sulfone

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. 

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). 

Although some oxidation of biotin to form biotin sulfoxides had been noted,and the sulfones of biotin and bisnorbiotin were isolated from cultures of the bacteria grown on the d-sulfoxide, growth experiments indicated that the thiolanyl S must be at the level of sulfide to be extirpated. As with lipoate, details of the metabolic events that lead to release of S fragments are lacking however, we have recently isolated methyl thioacetate as a volatile metabolite. 

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. 

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