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.
Normal and Abnormal Intestinal Absorption by Humans
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
As shown in Figure 12.1, intestinal absorption essentially involves the transport of nutrients from digested food and water from the gut lumen, across the intestinal epithelium, into the lymph or venous blood. Basic mechanisms of absorption into an intestinal cell are by three different mechanisms: simple diffusion, facilitated diffusion, and active transport. Diffusion does not use metabolic energy, and the solute is not transported against a gradient. It does not need a transport protein and velocity vs. substrate concentration is linear. Facilitated diffusion involves a transport protein, demonstrates substrate specificity, and the reaction is saturable. The solute is not transported against a gradient and does not need metabolic energy. Active transport involves transport proteins and demonstrates substrate specificity. Transport is against a concentration gradient and metabolic energy is necessary.
Mitochondria and Embryo Viability
Carlos Simón, Carmen Rubio in Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
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).
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.
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.
Improved intestinal absorption of paclitaxel by mixed micelles self-assembled from vitamin E succinate-based amphiphilic polymers and their transcellular transport mechanism and intracellular trafficking routes
Published in Drug Delivery, 2018
Xiaoyou Qu, Yang Zou, Chuyu He, Yuanhang Zhou, Yao Jin, Yunqiang Deng, Ziqi Wang, Xinru Li, Yanxia Zhou, Yan Liu
As known, some proteins are responsible for intracellular transport of lipids, block copolymers and nanoparticles (Sakai-Kato et al., 2014). To elucidate the proteins involved in transport of objects in cells, the common method is to use siRNAs to down-regulate the expression of these specific transport proteins. However, we need to know the possible involved transport proteins at first. To date, little is known about proteins involved in transmembrane transport of nanoparticles. In order to screen the possible proteins involved in transport of transcellular transfer of the micelles, we hypothesized that some of these specific proteins might excrete from the cells following treatment of Caco-2 cell monolayers with micelles. Favorably, 12 proteins were collected from basolateral media, separated and analyzed, suggesting that these proteins might be related to transcellular transport of the micelles. Further studies are needed to verify whether these proteins are responsible for transcellular transport of the micelles by using siRNAs to down-regulate their expression. Notably, there are some other transport proteins not excreted from the cells to basolateral media. Furthermore, it was worth noting that there were correlations of the colocalization results of CLSM observation (Figure 5(B)) with the subcellular location of the collected proteins (Table 1). This finding is specific to these micelles. It will be necessary to elucidate the intracellular trafficking and proteins involved in transcytosis for different nanoparticles.
Related Knowledge Centers
- Facilitated Diffusion
- Macromolecule
- Membrane Protein
- Molecule
- Protein
- Active Transport
- Membrane Transport Protein
- Ion
- Biological Membrane
- Vesicular Transport Protein