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  • central nervou
  • In many patients, neurologic abnormalities such as seizures or mental retardation emerge at some point in early childhood, which are attributed to impaired transport of folates into the central nervous system. (bloodjournal.org)
  • This protein is also expressed in the brain and choroid plexus where it transports folates into the central nervous system. (nih.gov)
  • symporter
  • The first structures were of the glycerol 3-phosphate/phosphate exchanger GlpT and the lactose-proton symporter LacY, which served to elucidate the overall structure of the protein family and provided initial models for understanding the MFS transport mechanism. (wikipedia.org)
  • membrane
  • There is a prominent low-pH folate transport activity in the cells and/or membrane vesicles derived from these tissues which, in some cases, has been shown to be indicative of a proton-coupled folate transport process. (wikipedia.org)
  • hPCFT/HCP1 expressed transiently in human embryonic kidney 293 cells mediated the transport of folate at an acidic extracellular pH of 5.5 in a manner independent of Na + and insensitive to membrane potential, but its transport activity was absent at near-neutral pH. (aspetjournals.org)
  • A total of 4 of the mutated transporters resulted in a complete loss of transport function, primarily due to decreased protein stability and/or defects in membrane trafficking, while 2 of the mutated carriers manifested residual function. (bloodjournal.org)
  • The Transporter Classification Database (or TCDB) is an International Union of Biochemistry and Molecular Biology (IUBMB)-approved classification system for membrane transport proteins, including ion channels. (wikipedia.org)
  • In this model, the transporter opens to either the extracellular space or cytoplasm and simultaneously seals the opposing face of the transporter, preventing a continuous pathway across the membrane. (wikipedia.org)
  • organic
  • This interaction among ZMP, folates, and RFC, a folate/organic phosphate antiporter, is consistent with a classic exchange reaction. (aspetjournals.org)
  • An exception occurs with SLC family 21 (the organic anion transporting polypeptide transporters), which for historical reasons have names in the format SLCOnXm where n = family number, X = subfamily letter, and m = member number. (wikipedia.org)
  • influx
  • Influx has a Km range of 0.5 to 3µM for most folates and antifolates at pH 5.5. (wikipedia.org)
  • Extracellular ZMP inhibited RFC-mediated folate influx, and the presence of intracellular ZMP correlated with inhibition of folate efflux. (aspetjournals.org)
  • The data indicate that intracellular ZMP trans-stimulates folate influx and inhibits folate efflux, which, together, produce a marked augmentation in the net cellular folate level. (aspetjournals.org)
  • ZMP participates in an exchange reaction with folates that results in the trans-stimulation of folate influx and the suppression of folate efflux that together enhance net accumulation of folates and MTX within these cells. (aspetjournals.org)
  • Methotrexate
  • Folate transport mediated by hPCFT/hHCP1 at pH 5.5 was saturable with a K m of 1.67 μM and extensively inhibited by reduced folates, such as folinate, 5-methyltetrahydrofolate, and methotrexate (MTX). (aspetjournals.org)
  • Methotrexate (MTX), an analog of folate, has been widely used by oral administration in cancer chemotherapy. (aspetjournals.org)
  • functional
  • Depending on the SLC, these transporters are functional as either monomers or obligate homo- or hetero-oligomers. (wikipedia.org)
  • Many MFS transporters are thought to be dimers through in vitro and in vivo methods, with some evidence to suggest a functional role for this oligomerization. (wikipedia.org)
  • transport
  • Earlier studies demonstrated that the transport of folate in the intact small intestine occurs in a saturable manner with an acidic luminal pH optimum (pH 5.0-6.0) and is competitively inhibited by MTX ( Steinberg, 1984 ). (aspetjournals.org)
  • It is notable that the folate transport system has been suggested to be also shared by reduced folates, such as 5-methyltetrahydrofolate and folinate, with affinities comparable with that of folate. (aspetjournals.org)
  • Thus, the involvement of RFC1 in the intestinal folate transport is in question, and there has been an argument that some other transporter might be responsible for that. (aspetjournals.org)
  • When cells first accumulated ZMP and were then exposed to 5-iodotubercidin or AICAR-free buffer, the ZMP level markedly decreased and folate transport stimulation was abolished. (aspetjournals.org)
  • These studies establish that AICAR potentiation of folate transport is, in fact, RFC-mediated and that this is due to the buildup of the 5′-monophosphate derivative of AICAR, ZMP, with cells. (aspetjournals.org)
  • Folate transport at low pH was markedly impaired in transformed lymphocytes from 2 patients. (bloodjournal.org)
  • In many patients, neurologic abnormalities such as seizures or mental retardation emerge at some point in early childhood, which are attributed to impaired transport of folates into the central nervous system. (bloodjournal.org)
  • In 2 patients from the family previously reported, folate transport was assessed in transformed lymphocytes at low pH. (bloodjournal.org)
  • These protein energetically drive transport utilizing the electrochemical gradient of the target substrate (uniporter), or act as a cotransporter where transport is coupled to the movement of a second substrate. (wikipedia.org)
  • inhibition
  • In cancer therapy, inhibition of folate-dependent metabolic pathways has been achieved through the use of antifolates. (wayne.edu)
  • receptors
  • In addition, roles of various receptors, ATP powered pumps, channels, and transporters in transport of vital molecules in maintenance of homeostasis and normal body functions have been described in detail. (hindawi.com)
  • glycerol
  • The comparative study reveals different sets of enzyme genes amongst halophilic archaea, e.g. in glycerol degradation, pentose metabolism, and folate synthesis. (springer.com)
  • The first structures were of the glycerol 3-phosphate/phosphate exchanger GlpT and the lactose-proton symporter LacY, which served to elucidate the overall structure of the protein family and provided initial models for understanding the MFS transport mechanism. (wikipedia.org)
  • Functional
  • Many MFS transporters are thought to be dimers through in vitro and in vivo methods, with some evidence to suggest a functional role for this oligomerization. (wikipedia.org)
  • Depending on the SLC, these transporters are functional as either monomers or obligate homo- or hetero-oligomers. (wikipedia.org)
  • clinical
  • The published clinical research with acipimox (which is interesting) is usually of too short a duration to show weight changes, most studies usually last a few days or a couple of weeks. (blogspot.com)
  • blood
  • Total serum folate and red blood cell (RBC) folate drift apart with increasing age: whereas the former decreases (p = 0.01) RBC folate remains in the same bandwidth across all age groups (p = 0.12) A common reference interval combining age and gender strata can be obtained for vitamin B12 and holoTC, whereas a more differentiated approach seems warranted for serum folate and RBC folate. (biomedcentral.com)
  • importance
  • While one substrate of particular biological importance is often used to name the transporter or family, there may also be co-transported or leaked ions or molecules. (wikipedia.org)
  • variety
  • The CNS folate deficiency is associated with a variety of neurological findings including developmental delays and seizures. (wikipedia.org)
  • cases
  • While most MFS structures suggest large, rigid body structural changes with substrate binding, the movements may be small in the cases of small substrates, such as the nitrate transporter NarK. (wikipedia.org)