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Finding a Target
Published in Nathan Keighley, 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.
Body fluids and electrolytes
Published in Peate Ian, Dutton Helen, Acute Nursing Care, 2020
Facilitated diffusion is the passive movement of specific molecules, e.g., sodium ions, glucose and amino acids, down a concentration gradient (from high to low concentration), passing through the membrane, which requires the assistance of a specific carrier protein. So, rather like enzymes and their substrates, each carrier has its own shape and only allows one molecule (or one group of closely related molecules) to pass through, e.g., insulin to facilitate the transport of glucose into a cell (see Figure 3.5 in the previous chapter).
The cell
Published in Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella, Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella
With facilitated diffusion, carrier proteins move across the membrane in either direction and will transport a substance down its concentration gradient. In other words, substances are moved from an area of high concentration to an area of low concentration. This process is passive and requires no energy. An example of a substance transported by facilitated diffusion is glucose, which is a large, polar molecule. Because cells are constantly utilizing glucose to form ATP, there is a persistent concentration gradient for diffusion into the cell.
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).
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.
Drug delivery and targeting to brain tumors: considerations for crossing the blood-brain barrier
Published in Expert Review of Clinical Pharmacology, 2021
Yadollah Omidi, Nazanin Kianinejad, Young Kwon, Hossein Omidian
Of note, the main factors mediating the distribution of drug molecules to the CNS include the appropriate permeability balance of the BBB to drug molecules (influx), active efflux clearance of drugs, and the proper physicochemical properties (e.g. nonspecific binding to the brain tissue) that play key roles in drug partitioning and distribution into the CNS. As shown in Figure 10, the physiological volumes of the intrabrain compartments include the brain interstitial fluid (ISF) with a volume around 0.2 mL/g brain and the intracellular fluid (ICF) of the brain with a volume of about 0.8 mL/g brain of which the lysosomal compartment is about 0.01 mL/g brain [212]. Accordingly, the pH differences (i.e. 7.4 for blood, 7.3 for brain ISF, 7.0 for the cytosol of brain cells, and around 5.0 for lysosomes) can influence the equilibration of drug molecules. For example, basic drugs accumulate more within the low-pH organelles/compartments (lysosomes). Many drugs are subjected to a facilitated diffusion via solute carriers that can function bidirectionally, while they may also be prone to the efflux functions. Based on the PK principles, one can define the delivery of drugs by the following three distinctly different parameters (Figure 10). The first parameter is the rate of drug penetration to the brain based on the permeability surface area product (PS) – the so-called “net influx clearance”. The second factor is the extent of drug distribution in the CNS (i.e. the total concentration of unbound drug at a steady state in the brain, or the partition coefficient of the brain). The third is related to the intrabrain distribution of the drug molecules.