Entry into Cells

The behavior of metal ions in solution suggests that, in general, we may expect to find cationic, neutral, and anionic forms, the relative abundance of which will depend on the nature of the metal and the ionic environment. If proteins are present, then some fraction of the metal will be bound due to reactions with SH and other groups. The net charge on the metal or metal complex is expected to determine the types of pathways that are available to enter the cell, and it turns out that there are examples of each for metal ions. 

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Apelin receptors activate several signalling pathways including coupling through inhibitory G-proteins (G ) and Ras-independent activation of extracellular-regulated kinases (ERKs) via protein kinase C (PKC). The apelin receptor is one of number of G-protein-coupled receptors that can act as an alternative coreceptor for entry into cells of HIV and simian immunodeficiency vims (SIV) strains in human U87 cells expressing CD4 in vitro. Apelin peptides blocks entry of HIV but display different potencies, with apelin-36 being more effective than shorter sequences [3]. 

Inborn errors of fatty acid oxidation Carnitine entry into cells and mitochondria Certain enzymes of fatty acid oxidation... 

Such sugar-dendrimer complexes ( sugar balls ) have been used to inhibit the interactions of viruses with cell surfaces. Many viruses bind to particular carbohydrate residues on cell surfaces, which in turn facilitate their entry into cells and the resultant infection process. A virus particle presents a multi-dentate surface consisting of many carbohydrate-binding proteins able to interact with multiple cell-surface carbohydrates. The surface of a dendrimer that is modified with... 

The answer is b. (Hardman, p 1159.) Rifampin inhibits RNA synthesis in bacteria, mycobacteria, and chlamydiae by binding to the DNA-de pen dent RNA polymerase it also inhibits assembly of poxvirus particles. Rifampin is used as a single prophylactic agent for contacts of people with meningococcal or H. influenzae type b infections. Otherwise, it is not used alone because 1 in 10 organisms in a population exposed to rifampin will become resistant, possibly because of mutation or a barrier against rifampin s entry into cells. 

The evidence that empty intracellular Ca2+ stores can stimulate Ca2+ entry into cells via the CCE pathway is unassailable (Putney 1997). However, neither the signal responsible for communicating the state of the stores to the Ca2+ entry channel,... 

The concept of exploiting caveolae (e.g., in endothelial cells) in the development of drugs that gain entry into cells through caveolae-specific portals is one... 

An ability to penetrate lipid bilayers is a prerequisite for the absorption of drugs, their entry into cells or cellular organelles, and passage across the blood-brain barrier. Due to their amphiphilic nature, phospholipids form bilayers possessing a hydrophilic surface and a hydrophobic interior (p. 20). Substances may traverse this membrane in three different ways. 

Parenteral /32-agonists such as albuterol (salbuta-mol) increase the activity of the membrane sodium-potassium ATPase, and so increase potassium entry into cells. Nebulized or infused albuterol (salbutamol) significantly lowers serum potassium concentration over 5 hours. A suitable initial dose of nebulized albuterol is 5 mg in adults. It can provoke tremor and tachyarrhythmia, and it is desirable to monitor cardiac rhythm during nebulization. The combination of nebulized albuterol (salbutamol) with infusion of insulin + glucose is more effective than the infusion alone. 

Greber, U.F., M. Willetts, P. Webster, and A. Helenius, Stepwise dismantling of adenovirus 2 during entry into cells. Cell, 1993. 75(3) 477-86. 

Docosanol is a saturated 22-carbon aliphatic alcohol that inhibits fusion between the plasma membrane and the HSV envelope, thereby preventing viral entry into cells and subsequent viral replication. Topical docosanol 10% cream is available without a prescription application site reactions occur in approximately 2%. When applied within 12 hours of the onset of prodromal symptoms, five times daily, median healing time was shortened by 18 hours compared with placebo in recurrent orolabial herpes. 

TSome microbial pathogens have lectins that mediate bacterial adhesion to host cells or toxin entry into cells. The bacterium believed responsible for most gastric ulcers, Helicobacter pylori, adheres to the inner surface of the stomach by interactions between bacterial membrane lectins and specific oligosaccharides of membrane glycoproteins of the gastric epithelial cells... 

The small size of the plasmid (4,361 bp) facilitates its entry into cells and the biochemical manipulation of the DNA. 

Chylomicrons deliver tiiacylglycerols to tissues, where lipoprotein lipase releases free fatty acids for entry into cells. Triacylglycerols stored in adipose tissue are mobilized by a hormone-sensitive triacylglycerol lipase. The released fatty acids bind to serum albumin and are carried in the blood to the heart, skeletal muscle, and other tissues that use fatty acids for fuel. 

Most sugars are rapidly phosphorylated following their entry into cells. They are thereby trapped within the cells, because organic phosphates cannot freely cross membranes without specific transporters. An alternate mechanism for metabolizing a monosaccharide is to convert it to a polyol by the reduction of an aldehyde group, thereby producing an additional hydroxyl group. 

The magnesium ion has a smaller radius than Ca2+, a fact that may account for its more ready entry into cells. Mg2+ can often be replaced by Mn2+ with full activity for enzymes that require it. On the other hand, high concentrations of Ca2+ are often antagonistic to Mg2+. This antagonism is clearly seen in the effect of the two ions on irritability of protozoa. Both deficiency of magnesium and excess of calcium in the surrounding medium cause in-... 

Greber, U.F., Webster, P., Weber, J. and Helenius, A. (1996) The role of Hie adenovirus protease in virus entry into cells. EMBOJ., 15, 1766-1777. 

Kielian, M. and Jungerwirth, S. (1990) Mechanisms of enveloped virus entry into cells. Mol. Biol. Med., 7, 17-31. 

Transferrin is a single-chain glycoprotein that binds 2 g-atoms of ferric iron per mole of protein. The iron is chelated via tyrosyl and histidyl residues, and the complex is extremely stable at physiologic pH. The function of transferrin is to transport iron throughout the human organism, especially to the immature red cells, which cannot effectively acquire iron for the biosynthesis of hemoglobin unless it is presented to them in combination with transferrin. Specific transferrin receptors are present on the surface of such immature red cells as well as in all other tissues. Receptor-mediated endocytosis (see Chapter 9) is believed to be the main means of transferrin-bound iron entry into cells. Transferrin is also believed to be antimicrobial because it withholds iron from microorganisms. 

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