Transport riboflavin

Recently, Prasad et al. cloned a mammalian Na+-dependent multivitamin transporter (SMVT) from rat placenta [305], This transporter is very highly expressed in intestine and transports pantothenate, biotin, and lipoate [305, 306]. Additionally, it has been suggested that there are other specific transport systems for more water-soluble vitamins. Takanaga et al. [307] demonstrated that nicotinic acid is absorbed by two independent active transport mechanisms from small intestine one is a proton cotransporter and the other an anion antiporter. These nicotinic acid related transporters are capable of taking up monocarboxylic acid-like drugs such as valproic acid, salicylic acid, and penicillins [5], Also, more water-soluble transporters were discovered as Huang and Swann [308] reported the possible occurrence of high-affinity riboflavin transporter(s) on the microvillous membrane. 

Gastaldi G, Ferrari G, Verri A, Casirola D, Orsenigo MN, and Laforenza U (2000) Riboflavin phosphorylation is the crucial event in riboflavin transport by isolated rat entemcytes. Journal of Nutrition 130,2556-61. 

Kindi, G., and GastaLdi, G- (1997). Measurements and characteristics of intestinal riboflavin transport. MeiiwxSs Emymol. 280, Part J, 399-407. 

In A. gossypii kinetic studies of riboflavin import and excretion using riboflavin, auxotrophic and overproducing A. gossypii mutants indicated the presence of active riboflavin transport mechanisms in the fungus. Inhibition of riboflavin uptake by FMN or FAD led to an increase in the apparent riboflavin efflux in the early... 

Riboflavin, FMN, and FAD metabolism RibU/EcfAA T - riboflavin transporter Firmicutes 20-22 Genetics and uptake assays in Bacillus subtilis, 21,23, 24... 

PnuX - riboflavin transporter Actinobacteria 22 Cloned from Corynebacterium 24... 

Recently, studies have showed that the mechanism of riboflavin absorption in the small and large intestines involves an efficient and specific Na" -independent carrier (Said 2004 Said and Seetharam 2006). The absorption rate is proportional to dose (saturation level is achieved with about 25-30 mg) and riboflavin half-life is 1.1 h. Three human riboflavin transporters (hRFT), hRFT-1, hRFT-2 and hRFT-3, have been described, all of them being expressed in the human intestine. Very recently, Subramanian et al. (2011) suggested a predominant role for the hRFT-2 in riboflavin intestinal absorption. 

Subramanian, V.S., Subramanya, S.B., Rapp, L., Marchant, J.S., Ma, T.Y., and Said, H.M., 2011. Differential expression of human riboflavin transporters -1, -2, and -3 in polarized epithelia a key role for hRFT-2 in intestinal riboflavin uptake. Biochimica et Biophysica Acta. 1808 3016-3021. 

Inhibition of riboflavin transport across the Caco-2 monolayer by 2,4-dini-trophenol (DNP), reducing the cellular ATP agent, points toward the necessity of delivering energy. However, the initial phase of whole absorption process i.e. transport across the epithelium membrane) does not require a supply of metabolic energy and is a consequence of riboflavin s association with carrier protein which is presented on the brush-border membrane. In the next step, some of the riboflavin absorbed inside the enterocytes cytosol is phosphory-lated by flavokinase and converted by FAD synthetase—enzymes which require ATP molecules for their action (Gastaldi et al. 1999). 

Other studies also indicate a receptor-mediated endocytosis way of riboflavin transport across intestinal cells. This thesis came about from a result observed in a particular condition a slight absorption dependence on pH, which may suggest pH-dependent uncoupling of ligand-receptor interactions in receptor-mediated endocytosis (Foraker et al. 2003 Yamamoto et al. 2009). 

Huang and Swaan (2000) revealed that the receptor-mediated mechanism of riboflavin takes place in the nanomolar range of riboflavin concentrations, whereas carrier-mediated process dominates in the micromolar range. They observed the inhibition of basolateral-apical transport of riboflavin by the same substances as transferrin, which is the typical protein transported through receptor-mediated endocytosis, i.e. brefeldin A and nocodazole. Brefeldin A strongly increased apical to basolateral riboflavin transport, while nocodazole increased apical to basolateral and inhibited basolateral to apical flux of riboflavin. 

Relevant in making the maintenance of brain homeostasis possible is the third identified human riboflavin transporter hRFT3 (GPR172A), which is expressed in the brain and salivary gland. It has the same substrate specificity as hRFTl and hRFT2, and functional characteristics similar to those of hRFTl (Yao et al. 2010). 

A carrier-mediated process was recognized as the mechanism of riboflavin transport in every proposed model. 

Kansara, V., Pal, D., Jain, R., and Mitra, A.K., 2005. Identification and functional characterization of riboflavin transport in human-derived retinoblastoma cell line(Y-79) mechanism of cellular uptake and translocation. Journal of Ocular Pharmacology and Therapeutics. 21 275-287. 

Spector, R., 1982. Riboflavin transport by rabbit kidney slices characterization and relation to cyclic organic acid transport. Journal of Pharmacology and Experimental Therapeutics. 221 394—398. 

Yanagawa, N., Jo, O.D., and Said, H.M., 1997. Riboflavin transport by rabbit renal brush border membrane vesicles. Biochimica et Biophysica Acta. 1330 172-178. 

Yao, Y., Yonezawa, A., Yoshimatsu, H., Masuda, S., Katsura, T., and Inui, K., 2010. Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. Journal of Nutrition. 140 1220-1226. 

Burgess, C.M., Slotboom, D.J., Geertsma, E.R., et al. (2006) The riboflavin transporter RibU in Lactococcus lactis molecular characterization of gene expression and the transport mechanism. J Bacterial 188, 2752-2760. 

Gut riboflavin transport systems have been studied by partly isolated segments of the small intestine within an anesthetized animal by an isolated everted gut segment, or by vesicles , prepared from the brush border. ... 

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