Sodium-dependent multivitamin transporter

SMVT Sodium-dependent multivitamin transporter SVCT Sodium-dependent vitamin C transporter THTR High affinity thiamine transporter... 

Biotin is essential for cell proliferation. Peripheral blood mononuclear cells appear to take up biotin by a system that is distinct from the sodium-dependent multivitamin transporter that is responsible for intestinal and renal uptake of biotin (Section 11.1). In response to mitogenic stimuli the uptake of biotin increases several-fold, with no change in the activity of the sodium-dependent transporter. At the same time, there is an increase in the rate of expression of methylcrotonyl CoA, propionyl CoA carboxylases, and holocarboxylase... 

Prasad PD and Ganapathy V (2000) Structure and function of mammalian sodium-dependent multivitamin transporter. Current Opinion in Clinical Nutrition and Metabolic Care 3, 263-6. 

Zempleni J, Steven Stanley J, and Mock DM (2001) Proliferation of peripheral blood mononuclear cells causes increased expression of the sodium-dependent multivitamin transporter gene and increased uptake of pantothenic acid./owma/ of Nutritional Biochemistry 12, 465-73. 

Biotin in the diet is largely protein bound, and digestion of these proteins by gastrointestinal enzymes produces biotinyl peptides, which may be further hydrolyzed by intestinal bio-tinidase to release biotin. Avidin, a protein found in raw egg whites, binds biotin tightly and prevents its absorption. The peptide biocytin (e-N-biotinyl lysine) is resistant to hydrolysis by proteolytic enzymes in the intestinal tract but together with biotin is readily absorbed. A biotin carrier, the sodium-dependent multivitamin transporter (SMVT)... 

Pantothenic acid is taken in as dietary CoA compounds and dCphosphopantetheine and hydrolyzed by pyrophosphatase and phosphatase in the intestinal lumen to dephospho-CoA, phosphopantetheine, and pantetheine. This is further hydrolyzed to pantethenic acid. The vitamin is primarily absorbed as pantothenic acid by a saturable process at low concentrations and by simple diffusion at higher ones. The saturable process is facilitated by a sodium-dependent multivitamin transporter, for which biotin and lipoate compete. After absorption, pantothenic acid enters the circulation and is taken up by cells in a manner similar to its intestinal adsorption. The synthesis of CoA from pantothenate is regulated by pantothenate kinase, which itself is subject to negative feedback from the products CoA and acyi-CoA. The steps involved were outlined above. Pantothenic acid is excreted in the urine after hydrolysis of CoA compounds by enzymes that cleave phosphate and the cys-teamine moieties. Only a small fraction of pantothenate is secreted into milk and even less into colostrum. 

Vadlapudi AD, Vadlapatla RK, Pal D, Mitra AK. Biotin uptake by T47D breast cancer cells functional and molecular evidence of sodium-dependent multivitamin transporter (SM VT). Int J Pharm 2013 441 535-43. 

Lipoic acid may be administered to treat heavy metal intoxication, to reduce signs of diabetic neuropathy, and to enhance glucose disposal in patients with noninsulin-dependent diabetes mellitus. Lipoic acid is structurally similar and competes with biotin for cellular uptake by a sodium-dependent multivitamin transporter (SMVT) and, perhaps, displaces biotin from HLCS. Chronic administration of pharmacological doses of lipoic acid decreases the activities of PC and MCC in rat liver to 64-72% of controls (Zempleni et al. 2009). 

The sodium-dependent multivitamin transporter is the quantitatively most important biotin transporter in the majority of human tissues. The monocarboxylate transporter 1 may play a specialized role in biotin uptake in cells from the lymphoid lineage. 

Biotin deficiency may be caused by inborn errors on other proteins involved in biotin homeostasis biotidinase, the sodium-dependent multivitamin transporter and holocarboxylase synthetase (Zempleni et al. 2008). A congenital deficiency of either of these proteins may create impairments in essential metabolisms, causing clinical signs with various intensities. 

Pacheco-Alvarez D, Solorzano-Vargas RS, Gonzales-Noriega A, Michalak C, Zempleni J, and Leon-Del Rio. Biotin availability regulates expression of the sodium-dependent multivitamin transporter and the rate of biotin uptake in Hep G2 cells. Mol. Genet. 

CRISP, S. E. R. H., CAMPGREALE, G., WHITE, B. R., TGGMBS, C. F., GRIFEIN, J. B., SAID, H. M., ZEMPLENI, J. (2004) Biotin supply affects rates of cell proliferation, biotinylation of carboxylases and histones, and expression of the gene encoding the sodium-dependent multivitamin transporter in JAr choriocarcinoma cells. Eur. J. Nutr., 43, 23-31. 

DEY, S., SUBRAMANIAN, V. S CHATTERJEE, N. S., RUBIN, S. A., SAID, H. M. (2002) Characterization of the 5 regulatory region of the human sodium-dependent multivitamin transporter, hSMVT. Biochim. Biophys. Acta, 1574, 187-192. 

Two biotin transporters have been described a multivitamin transporter present in many tissues and a biotin transporter identified in human lymphocytes. In 1997, Prasad and coworkers discovered a Na" "-coupled, saturable, structurally specific transporter present in human placental choriocarcinoma cells that can transport pantothenic acid, lipoic acid, and biotin. This sodium-dependent multivitamin transporter has been named SMVT and is widely expressed in human tissues. Studies by Said and coworkers using RNA interference specific for SMVT provide strong evidence that biotin uptake by Caco-2 and HepG2 cells occurs via SMVT thus, intestinal absorption and hepatic uptake are likely mediated by SMVT. The biotin transporter identified in lymphocytes is also Na coupled, saturable, and structurally specific. Studies by Zempleni and coworkers provide evidence in favor of monocarboxylate transporter-1 as the lymphocyte biotin transporter. 

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