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The Cell Membrane in the Steady State
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
A uniporter is a transmembrane protein that facilitates diffusion of a substance down a concentration gradient, without ATP hydrolysis, but at a rate that can be far higher than that of passive diffusion for that substance, the energy being derived from the concentration gradient of the transported substance. Glucose and amino acids are transported across the plasma membrane in this manner, the concentration gradient being established in these cases because these substances are used up in cell metabolism. The inner mitochondrial membrane has an efficient Ca2+ uniporter that allows a fast uptake of Ca2+ by mitochondria. This type of movement is referred to sometimes as facilitated transport, or facilitated diffusion. In a uniporter, a specific protein transports a particular substance by undergoing a conformational change, much like that illustrated in Figure 2.5 for the Na+-K+ pump but without ATP hydrolysis.
Biological Transport
Published in Lelio G. Colombetti, Biological Transport of Radiotracers, 2020
In a second process, the entry of certain solutes into the cell has been found to be facilitated by a mediator, even though the solute does not become more concentrated inside the cell than outside. In the simple diffusion case, the rate of entry depends directly upon the concentration of solute outside the cells, while in the facilitated transport, a large concentration of solute could saturate the transport mediator and cause the proportionality to be broken. Some evidence of the facilitated transport mechanism was obtained by Ege and Cori.18,19
Pharmacokinetics and Pharmacodynamics of Drugs Delivered to the Lung
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Stefanie K. Drescher, Mong-Jen Chen, Jürgen B. Bulitta, Günther Hochhaus
It is assumed that for lipophilic corticosteroids the dissolution step is rate limiting, since their penetration (e.g. diffusion) across lipophilic membranes is fast (Lanman et al. 1973; Burton and Schanker 1974a, 1974b, 1974c; Gardiner and Schanker 1974). With absorption of low-molecular weight, hydrophilic drugs can also be very efficient, which leads to a short pulmonary residence time; these drug are often absorbed through water filled channels (Enna and Schanker 1972; Lanman et al. 1973; Burton et al. 1974; Schanker and Burton 1976). Facilitated transport might also be important for membrane permeability and drug absorption (Enna and Schanker 1973; Gardiner and Schanker 1974; Byron et al. 1994). For several less lipophilic drugs, including beta-2-adrenergics and antimuscarinics, membrane interactions seem to be more important for retaining the drug in the lung. This interaction might be specific, as in the case of retention via specific interactions of the drug molecule with lung components as seen for long acting beta-2-adrenergic drugs, trapping of drugs in lysosomes (Borghardt et al. 2016a); alternatively, formation of lipophilic esters may slow down or prevent absorption into the systemic circulation (Tunek et al. 1997).
Design and assembly of a nanoparticle, antibody, phthalocyanine scaffold for intracellular delivery of photosensitizer to human papillomavirus-transformed cancer cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2023
Elvin Peter Chizenga, Heidi Abrahamse
Intracellular targeting using large molecules like Abs and other proteins, asintroduced earlier, has for many years been regarded as undoable because of the need for facilitated transport by the cells using energy, which results in the failure especially of normal physiological cells to take up larger molecules through their membrane. Natural Abs are mostly limited in this regard due to their large size and certainly other physiognomies. Hence, intracellular targeting using Abs has been considered unviable. However, as seen in this study and supported by others [17,18], intracellular targets so called “undruggables” are actually “druggable.” They just might be 'difficult to drug’ or 'yet to be drugged.’ In theirhe natural state, physiological macromolecules that are absolutely required for intracellular function have properties and/or conformations that enable them to pass through membranes. Abs designed for intracellular antigens (Ags) are internalized by varying active transport mechanisms involving endondocytic vesicles, such as endosomes or phagosomes [19], receptor-mediated entry [20], caveolae/raft-dependent endocytosis [21], and/or clathrin-dependent endocytosis [22]. These Abs are able to pass through membranes to localize inside the cells and also undergo transcytosis within the cells to move around the cytoplasm. Moreover, AuNP facilitates the cellular uptake of large molecules, including mAbs as demonstrated in HeLa cells, which internalized anti-mitochondrial mAbs using protein-facilitated cell penetration by endocytosis [23].
Fatty acids produced by the gut microbiota dampen host inflammatory responses by modulating intestinal SUMOylation
Published in Gut Microbes, 2022
Chaima Ezzine, Léa Loison, Nadine Montbrion, Christine Bôle-Feysot, Pierre Déchelotte, Moïse Coëffier, David Ribet
Fatty acids regulate intestinal cell activities by various mechanisms. They may bind to specific receptors expressed on intestinal cells, such as GPR41/FFAR3, GPR43/FFAR2, and GPR109A, and activate various signaling pathways.6 Fatty acids may also directly enter into intestinal cells by passive diffusion or by facilitated transport. Fatty acids are weak organic acids, which exist in solution either as acidic or basic forms. Only the acidic (uncharged) forms may passively diffuse across the plasma membrane, whereas the basic (negatively charged) forms are uptaken via specific transporters such as MCT1, MCT4, SMCT1, or SMCT2.7 Once in intestinal cells, fatty acids participate to the cell metabolism. For example, colonocytes were shown to use butyrate as a major energy source or, alternatively, isobutyrate when butyrate availability is low.8,9 Finally, fatty acids may regulate intestinal cell activities by interfering with post-translational modifications such as neddylation.10,11 The impact of fatty acids on other ubiquitin-like modifications in intestinal cells has not been described yet.
Clarithromycin laurate salt: physicochemical properties and pharmacokinetics after oral administration in humans
Published in Pharmaceutical Development and Technology, 2019
Bashar A. Alkhalidi, Hatim S. AlKhatib, Mohammad Saleh, Saja Hamed, Yasser Bustanji, Nader Al Bujuq, Naji Najib, Susana Torrado-Susana, Al-Sayed Sallam
It seems that the behavior of lauric acid in vivo was more than just a former hydrophobic salt but also an absorption enhancement. Fatty acids were reported earlier as effective agents to improve bioavailability (Rezhdo et al. 2016) by various mechanisms. Maggio and Lucy (1975) found that the degree of disorder of the membrane corresponds with the flexibility of the acyl chains of fatty acids, especially the cis-unsaturated and short carbon chain fatty acids. Green and Hadgraft (1987) reported a facilitated transport mechanism that was established when oleic acid and lauric acids were incorporated into an artificial membrane. Aungst and Hussain (1992) reported an increase in the bioavailability of propranolol laurate compared to propranolol base which was explained by the rapid initial delivery of high concentrations to the liver saturated for first pass metabolism and/or the increase in the splanchnic and hepatic blood flow in response to propranolol laurate or dissociated lauric acid.