Cell and molecular aspects of human intestinal biotin absorption.

Humans cannot synthesize biotin and thus must obtain this vitamin from exogenous sources. The intestine is exposed to 2 sources of biotin: a dietary source and a bacterial source, which is normal microflora of the large intestine. Dietary protein-bound biotin is converted to free biotin prior to absorption. Absorption of free biotin in the small and large intestine involves a saturable and Na(+)-dependent carrier-mediated process that is shared with pantothenic acid and lipoate. For this reason, the involved transport system is referred to as the sodium-dependent multivitamin transporter (SMVT); in humans, it is designated as hSMVT. The hSMVT system has been cloned, demonstrated to be exclusively expressed at the apical membrane of enterocytes, and shown, by means of gene-specific short interfering RNA, to be the main biotin uptake system that operates in human intestinal epithelial cells. The 5'-regulatory region of the hSMVT gene has also been cloned and characterized both in vitro and in vivo. Further, the human intestinal biotin uptake process was adaptively up-regulated in biotin deficiency via a transcriptionally mediated mechanism(s) that involves Kruppel-like factor 4 sites. Studies on cell biology of hSMVT have shown a region in the cytoplasmic C-terminal domain of the polypeptide to be essential for its targeting to the apical membrane domain of epithelial cells. Intracellular trafficking of the hSMVT protein appears to involve distinct trafficking vesicles that require an intact microtubules network and the motor protein dynein for their mobility.