Gastrointestinal Tract as a Major Route of Pharmaceutical Administration
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Facilitated diffusion or facilitated transport is a protein carrier-mediated process by which molecules or ions can pass through the cell wall via specific transmembrane integral proteins. If a particle is not lipid soluble and is too large to pass through the pores of the cell wall, then it uses the help of a carrier protein. An example is glucose, which is not only too large to enter the membrane but also insoluble in lipids. The process involves binding of the substance to a specific carrier protein. The complex binds to a receptor site within the cell which transports the entire complex through the cell membrane and releases it on the other side. Facilitated transport does not directly require chemical energy from ATP hydrolysis in the transport step itself; rather, molecules and ions move down their concentration gradient reflecting its passivity. It differs from simple diffusion in that it relies on molecular binding with a carrier protein, is saturable, and is significantly temperature dependent (Bauer and Metzler, 2013; Gomez and Klumpp, 2016).
Finding a Target
Nathan Keighley in Miraculous Medicines and the Chemistry of Drug Design, 2020
Transport across plasma membranes is a crucial part of a cells existence. The cell membrane presents a barrier to most polar molecules, which is important for maintaining concentrations of solutes in the cytoplasm. Likewise, the membrane-bound organelles within the cell can have a specific concentration of molecules contained within; different from that of the cytoplasm or extracellular medium. However, critical substances required by the cell must have a means of entering the cell as well as the removal of waste products. This is where the key role of transmembrane transport protein comes into fruition; as they are responsible for transporting these water-soluble molecules across the plasma membrane. A given transport protein will be responsible for assisting the movement of closely related groups of organic molecule, or a specific ion, across the membrane. There are two classes of membrane transport protein: carrier proteins and channel proteins. Carrier proteins have moving parts, activated by the chemical energy source ATP, that mechanically move small molecule across the membrane. This is known as active transport. Channel proteins form a narrow hydrophilic pore that enables the passive movement of inorganic ions, known as facilitated diffusion. By these mechanisms, the cell can create large differences in composition between the internal environment and extracellular medium. This is essential for specialised cells to perform their role in the body.
Electrolytes: Their function and movement
Bernie Garrett in Fluids and Electrolytes, 2017
Facilitated diffusion is another form of passive transport, but here the movement of some molecules (such as fatty acids or polar ions, which move less easily) is facilitated by carrier proteins. Larger molecules, especially those that are not soluble in lipids (such as amino acids), do not pass so easily through cell membranes. Likewise, polarized molecules or charged ions (e.g., glucose and sodium and chloride ions) are water soluble, but cannot easily diffuse across cell membranes due to the hydrophobic nature of the cell membrane itself, which repels them. Carrier proteins (also called permeases or transporters) bind to specific molecules and undergo a series of configuration changes that have the effect of carrying the solute to the other side of the cell membrane. The carrier then discharges the solute and reorients in the membrane back to its original state. A specific carrier will transport only a small range of related molecules (see Figure 3.4).56
Anti-infective treatment of brain abscess
Published in Expert Review of Anti-infective Therapy, 2018
Jacob Bodilsen, Matthijs C. Brouwer, Henrik Nielsen, Diederik Van De Beek
The dynamics of molecule exchange across the BBB and blood-CSF barrier is a complex and tightly regulated process maintained by both passive and active mechanisms. Depending on the concentration gradient, simple passive diffusion of very small (e.g. H2O) and/or lipophilic substances may occur across the lipid membranes of the cerebrovascular endothelial cells. This diffusion is increased at the extremes of age and by meningeal inflammation. In the few areas without tight junctions (~ 0.02% of the total cerebral vascular endothelial surface area), larger and more hydrophilic molecules are able to reach the CNS by filtration. Facilitated diffusion denotes transport of specific substances across the BBB by certain ‘helper’ molecules without the use of energy. This mechanism can sometimes be saturated, may be subject to substrate competition, and stops once equilibrium has been reached.
Advance in placenta drug delivery: concern for placenta-originated disease therapy
Published in Drug Delivery, 2023
Miao Tang, Xiao Zhang, Weidong Fei, Yu Xin, Meng Zhang, Yao Yao, Yunchun Zhao, Caihong Zheng, Dongli Sun
Transporter-mediated uptake is divided into facilitated diffusion and active transport. Facilitated diffusion allows certain compounds to cross the placenta without energy. Active transport is an energy-dependent process that usually proceeds against a concentration gradient. The major superfamily of transporters found in the placenta are the SLC and ABC transporters (Al-Enazy et al., 2017; Staud et al., 2012). For instance, organic anion transporters are a family of transporters in the placenta, mediating transport in the maternal-fetal interface for metabolites, waste products, and hormones (Lofthouse et al., 2018). Similarly, transporters such as amino acid transporters, glucose transporters, and transferrin can deliver specific substrates across the placenta (Illsley, 2000; Parkkila et al., 1997). For example, iron is transported across the placenta through transferrin receptor-mediated endocytosis (Parkkila et al., 1997).
Influences of different sugar ligands on targeted delivery of liposomes
Published in Journal of Drug Targeting, 2020
Changmei Zhang, Zhong Chen, Wenhua Li, Xiaoying Liu, Shukun Tang, Lei Jiang, Minghui Li, Haisheng Peng, Mingming Lian
The movement of glucose in the blood or tissue is mediated by facilitative Glucose Transporter (GLUT) on cell membrane. GLUT is a kind of carrier protein embedded on the cell membrane. It transports glucose along the concentration gradient by using a way of facilitated diffusion without consuming energy. Therefore, GLUT can be specifically identified and bound by glucose or glycoconjugate [3]. The specific substrates of GLUT include glucose, galactose, mannose and their derivatives. These substrates can be modified relevant ligand complexes, which will occur cluster and invagination, then be swallowed by cells into lysosomes to release the drug at last [4]. Therefore, conjugation of some different ligands on the surface of liposome can achieve the purpose of active targeted drug delivery and improve the therapeutic effect of drugs.
Related Knowledge Centers
- Carbon Dioxide
- Diffusion
- Lipid Bilayer
- Oxygen
- Phospholipid
- Transmembrane Protein
- Active Transport
- Passive Transport
- Biological Membrane
- Adenosine Triphosphate