Wang K S, Mock N I, Mock D M
Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, AR 72202-3591, USA.
J Nutr. 1997 Nov;127(11):2212-6. doi: 10.1093/jn/127.11.2212.
Bisnorbiotin and biotin sulfoxide are the major catabolites of biotin for humans, swine, and rats. Increased urinary excretion of bisnorbiotin, biotin sulfoxide, or both have been observed during pregnancy and in patients treated with certain anticonvulsants. We sought more insight into the sites and mechanisms of biotin catabolism by exposing rats in vivo to compounds known to induce classes of enzymes that were candidates to catalyze the biotransformations. Rats were treated with the anticonvulsants phenytoin, phenobarbital, and carbamazepine, the steroid hormones dexamethasone and dehydroepiandrosterone, and the peroxisome proliferators clofibrate and di(2-ethylhexyl)phthalate. [14C]Biotin was injected intraperitoneally at physiologic doses in treated rats and control rats; HPLC and radiometric flow detection were used to specifically identify and quantify [14C]biotin and its metabolites in urine. Treatment effects were assessed by the change in the urinary excretion of [14C]bisnorbiotin and [14C]biotin sulfoxide in response to administration of [14C]biotin. No significant changes resulted from treatment with any of the anticonvulsants. With the steroid hormones and the peroxisome proliferators, [14C]bisnorbiotin excretion increased significantly. These results indicate that biotin is converted into bisnorbiotin in the liver and that this conversion likely occurs in peroxisomes or mitochondria or both via beta-oxidative cleavage, and, in contrast to responses in humans, the enzymes responsible for the formation of biotin sulfoxide in rats are not induced by the anticonvulsants examined here.
双降生物素和生物素亚砜是人类、猪和大鼠生物素的主要分解代谢产物。在孕期以及接受某些抗惊厥药物治疗的患者中，观察到双降生物素、生物素亚砜或两者的尿排泄量增加。我们通过在体内给大鼠注射已知可诱导催化生物转化的酶类的化合物，来深入了解生物素分解代谢的部位和机制。给大鼠分别用抗惊厥药物苯妥英、苯巴比妥和卡马西平、甾体激素地塞米松和脱氢表雄酮以及过氧化物酶体增殖剂氯贝丁酯和邻苯二甲酸二（2-乙基己基）酯进行处理。给处理过的大鼠和对照大鼠腹腔注射生理剂量的[14C]生物素；使用高效液相色谱法和放射性流量检测来特异性鉴定和定量尿液中的[14C]生物素及其代谢产物。通过给予[14C]生物素后[14C]双降生物素和[14C]生物素亚砜尿排泄量的变化来评估处理效果。任何一种抗惊厥药物处理均未导致显著变化。使用甾体激素和过氧化物酶体增殖剂后，[14C]双降生物素的排泄显著增加。这些结果表明，生物素在肝脏中转化为双降生物素，并且这种转化可能通过β-氧化裂解在过氧化物酶体或线粒体或两者中发生，而且与人类的反应不同，本文所检测的抗惊厥药物不会诱导大鼠中负责生物素亚砜形成的酶。
