BIOTIN BIOTRANSFORMATION TO BISNORBIOTIN IS ACCELERATED BY SEVERAL PEROXISOME PROLIFERATORS AND STEROID-HORMONES IN RATS

Bisnorbiotin and biotin sulfoxide are the major catabolites of biotin for humans, swine, and rats, Increased urinary excretion of bisnorbiot in, biotin sulfoxide, or both have been observed during pregnancy and in patients treated with certain anticonvulsants. We sought more insig ht into the sites and mechanisms of biotin catabolism by exposing rats in vivo to compounds known to induce classes of enzymes that were can didates to catalyze the biotransformations, Rats were treated with the anticonvulsants phenytoin, phenobarbital, and carbamazepine, the ster oid hormones dexamethasone and dehydroepiandrosterone, and the peroxis ome proliferators clofibrate and di(2-ethylhexyl)phthalate. [C-14]Biot in was injected intraperitoneally at physiologic doses in treated rats and control rats; HPLC and radiometric flow detection were used to sp ecifically identify and quantify [C-14]biotin and its metabolites in u rine, Treatment effects were assessed by the change in the urinary exc retion of [C-14]bisnorbiotin and [C-14]biotin sulfoxide in response to administration of [C-14]biotin, No significant changes resulted from treatment with any of the anticonvulsants, With the steroid hormones a nd the peroxisome proliferators, [C-14]bisnorbiotin excretion increase d significantly, These results indicate that biotin is converted into bisnorbiotin in the liver and that this conversion likely occurs in pe roxisomes or mitochondria or both via beta-oxidative cleavage, and, in contrast to responses in humans, the enzymes responsible for the form ation of biotin sulfoxide in rats are not induced by the anticonvulsan ts examined here.