Biotin transport

Ng, K.-Y. and Borchardt, R.T., Biotin transport in a human intestinal epithelial cell line (Caco-2), Life Sci., 53, 1121, 1993. 

Receptors and Transport Systems Affinity labeling of receptors, 46, 572 nicotinic acetylcholine receptors, 46, 582 )8-adrenergic receptors, 46, 591 opiate receptors, 46, 601 amino acid transport proteins, 46, 607 the biotin transport system, 46, 613. 

Two children with the late-onset form initially were reported as having a defect in intestinal transport of biotin. This conclusion was supported by finding low plasma biotin concentrations when these children were administered oral biotin compared to the concentrations of plasma biotin of unaffected control subject. In 1983, it was demonstrated that the primary biochemical defect in most patients with late-onset multiple carboxylase deficiency was a deficiency of serum biotinidase activity. The two children with a putative defect in intestinal biotin transport both were confirmed to have biotinidase deficiency. This disparity was reconciled by demonstrating that, in both cases, the children were biotin depleted at the time the biotin-loading studies were performed. Therefore, when the children initially were given biotin, although the vitamin was transported into the blood normally, it was rapidly taken up... 

Biotinidase activity in cerebrospinal fluid and the brain is very low. This suggests that the brain may not recycle biotin effectively and depends on biotin transported across the blood-brain barrier. Several symptomatic children who have failed to exhibit peripheral lactic acidosis or organic aciduria have had elevated lactate or organic acids in their cerebrospinal fluid. This compartmentalization of the biochemical abnormalities may explain why the neurological symptoms usually appear before other symptoms. Peripheral metabolic ketoacidosis and organic aciduria subsequently occur with prolonged metabolic compromise. 

Other proteins that interact with biotin including egg yolk biotinbinding proteins and biotin transport components from several systems including yeast, mammalian intestinal cells, and bacteria [70-73]. Note that although there are other proteins (e.g., fibropellins) that have a motif [DENY]-jc(2)-[KRI]-[STA]-x(2)-V-G-jc-[DN]-jc[FW]-T-[KR] in common with strept(avidin), most if not all of these protein do not bind biotin (http //www.expasy.org/prosite/). 

Chatterjee NS, Kumar CK, Ortiz A, Rubin SA, and Said HM (1999) Molecular mechanism of the intestinal biotin transport process. American Journal of Physiology 277, C605-13. 

Inborn errors of metabolism may be due to propionyl-CoA carboxylase deficiency, defects in biotin transport or metabolism, methylmalonyl-CoA mutase deficiency, or defects in adenosylcobalamin synthesis. The former two defects result in propionic acidemia, the latter two in methylmalonic acidemia. All cause metabolic acidosis and developmental retardation. Organic acidemias often exhibit hyperammonemia, mimicking ureagenesis disorders, because they inhibit the formation of N-acetylglutamate, an obligatory cofactor for carbamoyl phosphate synthase (Chapter 17). Some of these disorders can be partly corrected by administration of pharmacological doses of the vitamin involved (Chapter 38). Dietary protein restriction is therapeutically useful (since propionate is primarily derived from amino acids). Propionic and methylmalonyl acidemia (and aciduria) results from vitamin B12 deficiency (e.g., pernicious anemia Chapter 38). 

Biotin biosynthesis BioY/BioMN - biotin transporter... 

Baur, B., and Baumgartner, R. (1992). Na-t--dependent biotin transport into brush-border membrane vesicles from human kidney cortex. Pfluegers Arch. 422,499. 

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. 

Gralla, M., Camporeale, G., and Zempleni, J., 2008. Holocarboxylase synthetase regulates expression of biotin transporters by chromatin remodeling events at the SMVT locus. The Journal of Nutritional Biochemistry. 19 400 08. 

Vlasova, T.I., Stratton, S.L., Wells, A.M., Mock, N.I., and Mock, D.M., 2005. Biotin deficiency reduces expression of SLC19A3, a potential biotin transporter, in leukocytes from human blood. The Journal of Nutrition. 135 42-47. 

MANTHEY, K. C GRIFFIN, J. B ZEMPFENI, I. (2002) Biotin supply affects expression of biotin transporters, biotinylation of carboxylases, and metabolism of interleukin-2 in Jurkat cells. J. Nutr., 132, 887-892. 

Becker et al. specifically inactivated the biotin transport system of E. coli using biotin p-nitrophenyl ester. The lactose transport protein of E. coli was labeled by AT-bromoacetyl-/8-D-galactopyranosylamine. In the only reported attempt to isolate an affinity labeled protein, glucose 6-isothiocyanate, which is an affinity label for the glucose transport system in human erythrocytes, gave enough nonspecific labeling of other membrane proteins to render identification of the transport protein difficult. 

The above aflSnity labeling reagents were found to inhibit specifically the uptake of biotin, but not other nutrients, into yeast cells. From the reactivation studies, one can conclude that an essential cysteine or histidine residue was modified in the transport system. The biotinylated protein can be specifically adsorbed to avidin columns, and subsequent elution with thiols should yield biotin transport component (s) in an active form. 

This review is dedicated to Michel Gaudry (1942-1998), who contributed to many aspects in the research field of biotin biochemistry (biotin metabolism, biotin transport, biotin deficiency, and so on). His outstanding contribution to the previous editions of this book chapter is gratefully acknowledged. 

In rats, biotin transport is upregulated with maturation and by biotin deficiency. Although carrier-mediated transport of biotin is most active in the proximal small bowel of the rat, the absorption of biotin from the proximal colon is still significant, supporting the potential nutritional significance of biotin synthesized and released by enteric flora. Clinical studies have provided evidence that biotin is absorbed from the human colon, but studies in swine indicate that absorption of biotin from the hindgut is much less efficient than from the upper intestine furthermore, biotin synthesized by enteric flora is probably not present at a location or in a form in which bacterial biotin contributes importantly to absorbed biotin. Exit of... 

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. 

A child with biotin dependence due to a defect in the lymphocyte biotin transporter has been reported. The SMVT gene sequence was normal. The investigators speculate that lymphocyte biotin transporter is expressed in other tissues and mediates some critical aspect of biotin homeostasis. 

The relationship of these putative biotin transporters to each other and their relative roles in intestinal absorption, transport into various organs, and renal reclamation remain to be elucidated. 

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