Biotin is a bicyclic compound (Figure 1). One of the rings contains an ureido group (—N—CO—N—). The tetrahydrothiophene ring contains sulfur and has a valeric acid side chain. A significant proportion of biotin undergoes catabolism before excretion (Figure 1). Two principal pathways of biotin catabo-lism have been identified in mammals. In the first pathway, the valeric acid side chain of biotin is degraded by ^-oxidation. ^-Oxidation of biotin leads to the formation of bisnorbiotin, tetranorbiotin, and related intermediates that are known to result from ^-oxidation of fatty acids. The cellular site of this ^-oxidation of biotin is uncertain. Spontaneous (none-nzymatic) decarboxylation of the unstable /3-keto acids (/3-keto-biotin and ^-keto-bisnorbiotin) leads to formation of bisnorbiotin methylketone and tetranor-biotin methylketone; these catabolites appear in urine.
In the second pathway, the sulfur in the thiophane ring of biotin is oxidized, leading to the formation of biotin-l-sulfoxide, biotin-d-sulfoxide, and biotin sulfone. Sulfur oxidation may be catalyzed by a NADPH-dependent process in the smooth endoplas-mic reticulum. Combined oxidation of the ring sulfur and ^-oxidation of the side chain lead to metabolites such as bisnorbiotin sulfone. In mammals, degradation of the biotin ring to release carbon dioxide and urea is quantitatively minor. Biotin metabolism is accelerated in some individuals by anticonvulsants and during pregnancy, thereby increasing in urine the ratio of biotin metabolites to biotin.
Animal studies and studies using brush border membrane vesicles from human kidney cortex indicate that biotin is reclaimed from the glomerular filtrate against a concentration gradient by a saturable, Na+-depen-dent, structurally specific system, but biocytin does not inhibit tubular reabsorption of biotin. Subsequent egress of biotin from the tubular cells occurs via a basolateral membrane transport system that is not dependent on Na+. Studies of patients with biotinidase deficiency suggest that there may be a role for biotini-dase in the renal handling of biotin.
On a molar basis, biotin accounts for approximately half of the total avidin-binding substances in human serum and urine (Table 1). Biocytin, bisnorbiotin, bis-norbiotin methylketone, biotin-d,l-sulfoxide, and biotin sulfone account for most of the balance.
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