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Related Concept Videos

Active Transport01:14

Active Transport

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Active transport is a critical biological process that allows cells to move solutes against an electrochemical gradient. This process requires direct energy input and is characterized by its selectivity, saturability, and susceptibility to competitive inhibition.
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
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Pore Transport and Ion-Pair Transport01:17

Pore Transport and Ion-Pair Transport

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Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited  but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
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Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

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The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
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Carrier-Mediated Transport01:06

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Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
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Membrane Transporters01:31

Membrane Transporters

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Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
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Nonlinear Pharmacokinetics: Role of Transporters01:27

Nonlinear Pharmacokinetics: Role of Transporters

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A drug's nonlinear kinetics can be influenced by a diverse range of transporter proteins that serve as crucial players in drug distribution. These transporters, found within cells, can enhance or reduce local drug concentrations by facilitating the influx or efflux of drugs. For instance, the expression of xenobiotic transporters can be influenced by factors such as age and gender, potentially impacting the linearity of drug response.
Polymorphisms occurring in drug transporters can alter...
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Related Experiment Video

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Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
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Equilibrative nucleoside transporters-A review.

Rebba C Boswell-Casteel1, Franklin A Hays1,2,3

  • 1a Department of Biochemistry and Molecular Biology , University of Oklahoma Health Sciences Center , Oklahoma City , OK , USA.

Nucleosides, Nucleotides & Nucleic Acids
|October 21, 2016
PubMed
Summary

Equilibrative nucleoside transporters (ENTs) are crucial for drug efficacy. This review surveys studies on ENT genetics, interactions, and structure to understand their poorly understood molecular mechanisms.

Keywords:
Nucleoside transportequilibrative nucleoside transportermembrane proteinnucleobase transport

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Equilibrative nucleoside transporters (ENTs) are integral membrane proteins facilitating nucleoside and nucleobase transport.
  • Human ENTs (hENT1, hENT2) and non-mammalian orthologs are vital drug targets, influencing over 30 approved medications.
  • The precise molecular mechanisms governing ENT substrate recognition, binding, and transport remain largely unelucidated.

Purpose of the Study:

  • To review and synthesize current knowledge on the characterization of equilibrative nucleoside transporters.
  • To highlight the importance of ENTs as pharmaceutical targets.
  • To identify knowledge gaps in understanding ENT molecular mechanisms and substrate interactions.

Main Methods:

  • Literature review of studies on ENT genetics and function.
  • Analysis of research on permeant and inhibitor interactions with ENTs.
  • Survey of mutagenesis data and structural modeling approaches for ENTs.

Main Results:

  • ENTs are implicated in the transport of nucleosides, nucleobases, and various therapeutic analogs.
  • Genetic and mutagenesis studies have provided insights into ENT structure-function relationships.
  • Structural models offer a framework for understanding ENT-mediated transport and inhibition.

Conclusions:

  • ENTs are critical targets in drug development, necessitating a deeper understanding of their function.
  • Further research into ENT molecular mechanisms, substrate specificity, and inhibition is essential.
  • Integrating genetic, biochemical, and structural data will advance the field of nucleoside transporter research.