Normal and Abnormal Intestinal Absorption by Humans
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Due to the handling of electrolytes the small intestinal mucosal cell may be considered a polarized epithelial cell. The plasma membrane consists of the brush border facing the lumen and the basolateral membrane facing blood. The Na+-K+-ATPase is located exclusively on the basolateral membrane. Its function is to transport K+ into the cell and Na+ out of the cell. Both of these transport processes occur against a concentration gradient requiring metabolic energy. The Na+K+-ATPase is a transport protein as well as an ATPase. The energy released after ATP hydrolysis is used to energize the transport. The stoichiometry between the transported ions is 3 Na+: 2K+. This results in a Na+ gradient and a K+ gradient across the basolateral membrane.
Nutritional Ergogenic Aids: Introduction, Definitions and Regulatory Issues
Ira Wolinsky, Judy A. Driskell in Nutritional Ergogenic Aids, 2004
The cell membrane mainly consists of phospholipids and proteins. It is believed that ubiquinol plays an important role in protecting the membrane from lipid peroxidation (deterioration). It may act as either an independent antioxidant or a co-antioxidant with vitamin E and C.5,20 It has been suggested that ubiquinol may prevent both the initiation and propagation of lipid peroxidation, possibly because of its lipidphilic property and location in the membrane that allows its access to the proton-motive Q cycle. Vitamin E acts exclusively in inhibition of the propagation of lipid peroxidation.8 After quenching a free radical, CoQ10 can be recycled within plasma membranes and cytosol by quinone reductase.5 It has also been shown that ubiquinol provides protection for proteins and DNA against oxidative damage.8
Immune function of epithelial cells
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Many luminal materials, including hydrophilic nutrients, are transported by distinct transport proteins within apical and basolateral domains. Most often, apical transporters take advantage of the steep, electrochemical Na+ gradient (from extracellular to intracellular) to provide the driving force for absorption. The basolateral Na+-K+ATPase that maintains the Na+ gradient and pumps apically transported Na+ ions across the basolateral membrane is, therefore, essential to ongoing nutrient transport. Paracellular recycling of Na+ ions from the lamina propria to the lumen (via the tight junction, as discussed later) is essential, as the diet does not otherwise contain sufficient Na+ to support ongoing apical absorption. Solutes absorbed by apical transmembrane transport proteins cross the basolateral membrane via facilitated transporters that operate in a strictly concentration-dependent manner. This allows the basolateral transport proteins to drive nutrient absorption from the enterocyte cytoplasm toward the bloodstream when nutrients are being actively absorbed but to also operate in the reverse direction in order to bring nutrients into the enterocyte when none are present in the lumen, e.g., during fasting. Whether by vesicles or transmembrane transport proteins, transport of solutes, membranes, and cargo from one side, through the cell to the other side, is termed the “transcellular pathway” and is an energy-dependent process.
Roles of membrane lipids in the organization of epithelial cells: Old and new problems
Published in Tissue Barriers, 2018
As described above, the epithelial cell apical membrane and the basolateral membrane have different membrane protein and lipid distribution. Given that membrane proteins and lipids freely diffuse in the plane of cell membranes, some barrier that restricts free diffusion of membrane proteins and lipids are required at the boundary between the apical membrane and basolateral membrane to maintain epithelial polarity. As such a molecular mechanism, it is assumed that one of the cell adhesion apparatus, tight junction, which localizes to the boundary between apical membrane and basolateral membrane, is essential for the compartmentalization and maintenance of apical and basolateral membrane domains.17 To examine whether tight junction functions as such a fence, we established cultured epithelial cells lacking tight junctions by knocking out the main scaffolding proteins of tight junction, ZO-1 and ZO-2.
Modifying antibody-FcRn interactions to increase the transport of antibodies through the blood-brain barrier
Published in mAbs, 2023
Jason Tien, Dmitri Leonoudakis, Ralitsa Petrova, Vivian Trinh, Tetsuya Taura, Debapriya Sengupta, Lisa Jo, Angela Sho, Yong Yun, Eric Doan, Anita Jamin, Hussein Hallak, David S. Wilson, Jennifer R. Stratton
The exchange of many macromolecules, including immunoglobulins, between the circulatory system and the central nervous system (CNS) is restricted by the blood-brain barrier (BBB). The BBB is a biological interface formed, in part, by the tight and adherens junctions found between microvascular endothelial cells that line cerebral capillaries.1–3 Since these intercellular contacts prevent the free diffusion of most molecules across the BBB, the transport of macromolecules from the blood into the brain is tightly regulated by intracellular transport pathways found in the endothelial cells.4 Receptor-mediated transport (RMT) is one mechanism by which macromolecules can be transported across the BBB through a process termed transcytosis. In this process, ligands to be transported across the BBB specifically interact with receptors found on the luminal endothelial cell surface. Upon binding, the receptor-ligand complex is internalized by endocytosis and transported along the cytoskeleton in vesicles, which then fuses with the basolateral cell membrane. Through a SNARE-mediated exocytotic process, the ligand is ultimately released into the extracellular space of the brain parenchyma.5,6
Intracellular sequestration of HER2 via targeted subcellular peptide delivery
Published in Journal of Drug Targeting, 2018
Zachary F. Walls, Matthew Schwengels, Victoria Palau
In polarised cells, HER2 is localised to the basolateral membrane. Overexpression of HER2, however, causes a change in signalling that results in its ectopic expression on the apical membrane [8]. Depending on its localisation, HER2 shows different patterns of phosphorylation [9]. Phosphorylation of certain residues allows HER2 to activate particular cellular networks that favour survival [8,10]. HER2 overexpression has been observed in several types of cancer, and its activation contributes to the cancer’s metastatic potential [11]. Sequestration of HER2 within the secretory organelles of the cell would prevent its translocation to the cell surface and limit its ability to activate downstream messengers. AMIDST was configured for HER2 targeting with several independent and functional peptides (Figure 1). Combined with a HER2-interacting peptide and expressed as a single polypeptide, the AMIDST construct effectively delivers a peptide to the secretory organelles of the cell and alters the expression pattern and signalling efficiency of HER2.
Related Knowledge Centers
- Cytoplasm
- Extracellular Space
- Integral Membrane Protein
- Lipid Bilayer
- Membrane Fluidity
- Membrane Protein
- Phospholipid
- Biological Membrane
- Cell
- Cholesterol