Keratinocytes Join Forces with Immune Cells in the Prosecution of SMVT as a “False” Biotin Transporter

Abstract

SMVT, a sodium-dependent multivitamin transporter, was cloned in our laboratory first from rat placenta (Prasad et al, 1998) and subsequently from human placenta (Wang et al, 1999) and rabbit intestine (Prasad et al, 1999). This transporter mediates the active transport of three different water-soluble vitamins, namely biotin, pantothenate, and lipoate and the transport process is energized by a transmembrane electrochemical Na+ gradient (Prasad and Ganapathy, 2000). The Kt (Michaelis-Menten constant) values for biotin and pantothenate for transport via human SMVT are 5 and 2M, respectively. While the Kt value for pantothenate is only about 20 times higher than the plasma levels of this vitamin (0.1 M), the Kt value for biotin is four orders of magnitude higher than the plasma levels of biotin. The concentration of biotin in human blood is in the range of 0.5–2 nM (Mock et al, 1995). This raises the question as to whether SMVT can mediate the cellular uptake of biotin from the circulation efficiently at normal physiological concentrations of biotin. It was purely coincidental that in the same year that we cloned SMVT,Zempleni and Mock (1998) reported on the characteristics of biotin uptake in peripheral blood mononuclear cells which indicated the presence of a biotin transporter different from SMVT. The transporter in immune cells is Nadependent as is SMVT, but the Kt value for biotin in the case of the new transporter is 2.5 nM. Moreover, the transporter in immune cells does not interact with pantothenate or lipoate. Thus, the newly identified transporter is specific for biotin and operates with an affinity close to the plasma levels of biotin. This transporter is induced in immune cells during mitogen-induced proliferation (Zempleni and Mock, 2000). Interestingly, SMVT is also expressed in immune cells. Mock and his coworkers have hypothesized that while SMVT is needed in these cells for the cellular uptake of pantothenate, the newly identified transporter is predominantly responsible for biotin uptake under normal conditions (Zempleni and Mock, 2000). That the biotin-specific transporter identified in immune cells is distinct from SMVT is further substantiated by a recent report (Mardach et al, 2002) in which a biotin transport defect was seen in peripheral blood mononuclear cells in a patient associated with biotin dependency. The patient had no noticeable defect in the functional activity of SMVT.