MFS transporter

In general, hydrophobic cationic compounds are the preferred but not only substrates of MFS MDRs. MdfA from Escherichia coli [54] can extrude neutral compounds such as chloramphenicol in addition to various cationic compounds. MdfA was also shown to pump out an artificial substrate of P-galactosidase, isopropyl-P-o-galactoside [55]. 

GlpT have much more hydrophilic interiors. EmrD has not been characterized biochemically, and as such its structure was solved without a substrate. Nevertheless, comparison with much better characterized MFS MDRs (LmrP and MdfA) indicates that the EmrD cavity indeed might be involved in binding of multiple drugs [58]. 

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It is presently unclear whether all or only some ofthe MFPs interact with substrates during transport. The periplasmic portions ofthe MFPs associated with ABC and MFS transporters are fully exposed to the periplasm and are expected to come into a direct contact with substrates during translocation across the periplasm. In the case of RND pumps, however, the entire MFP seems to be engaged into protein-protein interactions without any freedom to bind substrates on its own [115, 118, 119]. 

ABC transporters in C. duhliniensis. CdMDRl encodes an MFS transporter [186]. ABCl and ABC2 encode ABC transporters in C. krusei [187],... 

FIGt 22-48 Transport mechanisms for separation membranes a) Viscous flow, used in UF and MF. No separation achieved in RO, NF, ED, GAS, or PY (h) Knudsen flow used in some gas membranes. Pore diameter < mean free path, (c) Ultramicroporoiis membrane—precise pore diameter used in gas separation, (d) Solution-diffusion used in gas, RO, PY Molecule dissolves in the membrane and diffuses through. Not shown Electro-dialysis membranes and metallic membranes for hydrogen. 

Currently, five different molecular classes of mdr efflux pumps are known [5], While pumps of the the ATP-binding cassette (ABC) transporter superfamily are driven by ATP hydrolysis, the other four superfamilies called resistance-nodulation-division (RND), major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), and small multidrag resistance transporter (SMR) are driven by the proton-motive force across the cytoplasmic membrane. Usually a single pump protein is located within the cytoplasmic membrane. However, the RND-type pumps which are restricted to Gram-negative bacteria consist of two additional components, a periplasmic membrane fusion protein (MFP) which connects the efflux pump to an outer... 

Semple, DM, Ebmeier KP, Glabus MF, O Carroll, RE and Johnstone, EC (1999) Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA ( ecstasy ) users. Br. J. Psychiatry 175 63-69. 

Figure 20-48 shows Wijmans s plot [Wijmans et al.,/. Membr. Sci., 109, 135 (1996)] along with regions where different membrane processes operate (Baker, Membrane Technology and Applications, 2d ed., Wiley, 2004, p. 177). For RO and UF applications, Sj , < 1, and c > Cl,. This may cause precipitation, fouling, or product denatura-tion. For gas separation and pervaporation, Sj , >1 and c < ci. MF is not shown since other transport mechanisms besides Brownian diffusion are at work. 

Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB. OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Dmg Metab Dispos 1999 ... 

Fei YJ, Kanai Y, Nussberger S, Ganapathy V, Leibach FH, Romero MF et al. Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 1994 368(6471) 563—566. 

Fromm MF, Kauffmann HM, Fritz P, Burk O, Kroemer HK, Warzok RW et al. The effect of rifampin treatment on intestinal expression of human MRP transporters. Am J Pathol 2000 157(5) 1575—1580. 

Fromm MF, Leake B, Roden DM, Wilkinson GR, Kim RB. Human MRP3 transporter identification of the 5 -flank-ing region, genomic organization and alternative splice variants. Biochim Biophys Acta 1999 1415(2) 369-374. 

Dephosphorylated synapsin inhibits axonal transport of MBOs in isolated axoplasm, while phosphorylated synapsin at similar concentrations has no effect [21]. When a synaptic vesicle passes through a region rich in dephosphorylated synapsin, it may be cross-linked to the available MF matrix by synapsin. Such cross-linked vesicles would be removed from fast axonal transport and are effectively targeted to a synapsin- and MF-rich domain, the presynaptic terminal. 

Properties of slow transport suggest molecular mechanisms. Information about mechanisms of slow axonal transport is relatively limited. They are energy-dependent and require an intact axonal cytoskeleton. Indirect evidence suggests that MTs play a critical role, because transport of NFs can be pharmacologically uncoupled from MT transport without eliminating slow transport [33]. In contrast, all agents that disrupt MTs appear to block slow transport of all components. While this does not rule out a role for the MF cytoskeleton in slow transport movements, MTs appear to provide motive force for other elements of the cytoskeleton. 

The Major Facilitator Superfamily (MFS) [95-97] is the largest secondary transporter family known in the genomes sequenced to date [98], These polytopic integral membrane proteins enable the transport of a wide range of solutes, including amino acids, sugars, ions, and toxins. Medically relevant members of the family include the bacterial efflux pumps associated with... 

Benet LZ, Wu CY, Hebert MF and Wacher VJ (1996) Intestinal Drug Metabolism and Anti-Transport Processes A Potential Paradigm Shift in Oral Drug Delivery. 

Collnot EM, Baldes C, Wempe MF, Hyatt J, Navarro L, Edgar KJ, Schaefer UF, Lehr CM (2006) Influence of vitamin E TPGS poly(ethylene glycol) chain length on apical efflux transporters in Caco-2 cell monolayers. J Control Release 111 35-40. 

Gorodeski GI, Romero MF, Hopfer U, Rorke E, Utian WH, and Eckert RL [ 1994] Human uterine cervical epithelial cells grown on permeable support—a new model for the study of differentiation and transepithelial transport. Differentiation 56 107-118... 

Gorodeski GI, Hopfer U, Eckert RL, Utian WH, De-Santis BJ, Rorke ER, and Romero MF [1994] ATP decreases acutely and reversibly transport through the paracellular pathway in human uterine cervical cells. Am J Physiol 266 0 692-0698... 

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