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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
The human body maintains a stable environment for its cells and tissues through a combination of physiological and biochemical processes. Cell membranes form a barrier to large molecules, allowing the cell to maintain a constant internal environment. Specific transport mechanisms are therefore required to transfer material in and out of the cell. Membranes contain many different proteins that actively or passively facilitate the movement of ions or molecules across membranes. Three major classes of transport protein are membrane channels, pumps and transporters.
Mitochondria and Embryo Viability
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Irene Corachan Garcia, Laura Iñiguez Quiles, Antonio Diez-Juan
Mitochondria play a critical role in the generation of metabolic energy in eukaryotic cells, using oxidative phosphorylation to derive energy (ATP) from carbohydrates and fatty acids. Mitochondria contain their own DNA, which encodes tRNAs, rRNAs, and some mitochondrial proteins (1). Ranging in size from 0.5 to 1.0 μm in diameter (2), these unique organelles have a double-membrane system consisting of inner and outer membranes separated by an intermembrane space (1). The outer mitochondrial membrane encloses the matrix (internal space) and contains a large number of proteins that form channels allowing small molecules to pass. The inner mitochondrial membrane, which is folded into structures (cristae) that increase the surface area, is less permeable, blocking the movement of ions and other small molecules. Both the inner and outer membranes contain specific transport proteins that can move molecules by a passive or active transport (2) (Figure 15.1).
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.
Mechanisms of Porphyromonas gingivalis to translocate over the oral mucosa and other tissue barriers
Published in Journal of Oral Microbiology, 2023
Caroline A. de Jongh, Teun J. de Vries, Floris J. Bikker, Susan Gibbs, Bastiaan P. Krom
In the case of being a risk factor for Alzheimer’s disease, in addition to the oral mucosa the bacterium would also need to pass the blood–brain barrier (BBB). Being composed of many cell types, the BBB is another challenging structural and functional barrier for microorganisms. The vessels in the brain do not contain any pores and its cells are tightly adhered together [87]. Transport across the barrier is regulated by specific transport proteins. This makes the blood–brain barrier highly selective and it is specialized to protect the brain against pathogens and toxins [88,89]. However, infection of the brain has been known to occur for various microorganisms. Multiple reviews about bacterial translocation of the BBB describe three of the four mechanisms described in the current review, including: disruption of adherence molecules, transcytosis and the ‘Trojan Horse’ mechanism via macrophages [90–92]. Research into the blood–brain barrier is challenging as it is difficult to represent this barrier in vitro.
Novel hyaluronic acid oligosaccharide-loaded and CD44v6-targeting oxaliplatin nanoparticles for the treatment of colorectal cancer
Published in Drug Delivery, 2021
Wenlong Du, Xiaoping Yang, Shenfu He, Jia Wang, Yuanxian Guo, Bangguo Kou, Yongjie Jiang, Pan Bian, Bingtai Li, Lanning Yin
Usually, oxaliplatin resistance is caused by ‘pump’ and ‘non-pump’ mechanisms. Pump mechanisms are triggered mainly by ATP-binding proteins, including P-gp1, breast cancer resistance protein, and multidrug resistance-related protein (Wang et al., 2015; Lu et al., 2017). This transmembrane transport protein can expel chemotherapeutic drugs from cells, thus reducing the intracellular drug concentration. Non-pump resistance mechanisms mainly include (1) overexpression of DNA repair systems, including mismatch repair and nucleotide excision repair (Kirschner and Melton 2010; Slyskova et al., 2018), which quickly repair damaged DNA during the G2/M phase of the cell cycle, thus producing drug resistance (Cohen et al., 2015); (2) inhibition of apoptosis, including upregulation of anti-apoptotic proteins such as Bcl2, NF-κB, and p53 (Ruiz de Porras et al., 2016; Smith and Macleod 2019); (3) detoxification via glutathione-S transferase and cytochrome P450 (Noda et al., 2012; Lin et al., 2016); and (4) multidrug resistance mediated by cancer stem cells, epithelial–mesenchymal transition, and altered tumor microenvironment (Zhang et al., 2015; Steinbichler et al., 2018; Chen et al., 2019).
Recent approaches to gout drug discovery: an update
Published in Expert Opinion on Drug Discovery, 2020
Naoyuki Otani, Motoshi Ouchi, Hideo Kudo, Shuichi Tsuruoka, Ichiro Hisatome, Naohiko Anzai
Membrane transport proteins, that is, transporters, are required for the hydrophilic urate to pass through cells. In the proximal tubules, for reabsorption, urate enters the cell by crossing the luminal membrane via the urate transporter 1 (URAT1) encoded by the SLC22A12 gene, and it moves across the basolateral membrane into the blood via the glucose transporter 9 (GLUT9) encoded by the SLC2A9 gene. Conversely, in the secretion of urate from blood to urine, the movement of urate into the proximal tubules via the vascular side membrane is performed by the organic anion transporter (OAT) 1 or OAT3, and its movement across the luminal side membrane to the tubular lumen for secretion into the urine is facilitated by the sodium-dependent phosphate transporter type 4 (NPT4) encoded by the SLC17A3 gene [6,25]. Other urate transporters such as ABCG2 that have been successively identified may also become new drug targets.