Misplaced Pages

#224775

71-396: 1XMI , 1XMJ , 2BBO , 2BBS , 2BBT , 2LOB , 2PZE , 2PZF , 2PZG , 3GD7 , 3ISW , 4WZ6 , 5D2D , 5D3E , 5D3F 1080 12638 ENSG00000001626 ENSMUSG00000041301 P13569 P26361 NM_000492 NM_021050 NP_000483 NP_066388 Cystic fibrosis transmembrane conductance regulator ( CFTR ) is a membrane protein and anion channel in vertebrates that

142-564: A hypotonic solution outside the cells and causing water to diffuse into the cells by osmosis. Several studies indicate that heterozygous carriers are at increased risk for various symptoms. For example, it has been shown that heterozygosity for cystic fibrosis is associated with increased airway reactivity, and heterozygotes may be at risk for poor pulmonary function. Heterozygotes with wheeze have been shown to be at higher risk for poor pulmonary function or development and progression of chronic obstructive lung disease . One gene for cystic fibrosis

213-618: A medical emergency . Measurement of electrolytes is a commonly performed diagnostic procedure, performed via blood testing with ion-selective electrodes or urinalysis by medical technologists . The interpretation of these values is somewhat meaningless without analysis of the clinical history and is often impossible without parallel measurements of renal function . The electrolytes measured most often are sodium and potassium. Chloride levels are rarely measured except for arterial blood gas interpretations since they are inherently linked to sodium levels. One important test conducted on urine

284-429: A voltage is applied, the electrolyte will conduct electricity. Lone electrons normally cannot pass through the electrolyte; instead, a chemical reaction occurs at the cathode , providing electrons to the electrolyte. Another reaction occurs at the anode , consuming electrons from the electrolyte. As a result, a negative charge cloud develops in the electrolyte around the cathode, and a positive charge develops around

355-417: A challenge in large part due to the difficulty in establishing experimental conditions that can preserve the correct ( native ) conformation of the protein in isolation from its native environment. Membrane proteins perform a variety of functions vital to the survival of organisms: The localization of proteins in membranes can be predicted reliably using hydrophobicity analyses of protein sequences, i.e.

426-419: A flexible lattice framework . Various additives are often applied to increase the conductivity of such systems. Solid ceramic electrolytes – ions migrate through the ceramic phase by means of vacancies or interstitials within the lattice . There are also glassy-ceramic electrolytes. Dry polymer electrolytes – differ from liquid and gel electrolytes in the sense that salt is dissolved directly into

497-413: A loss of the amino acid phenylalanine (F) at the 508th position on the protein. As a result, the protein does not fold normally and is more quickly degraded. The vast majority of mutations are infrequent. The distribution and frequency of mutations varies among different populations which has implications for genetic screening and counseling. Drug discovery for therapeutics to address CF in all patients

568-522: A receptor for Salmonella typhi bacteria to enter intestinal epithelial cells. Cystic fibrosis ΔF508 heterozygotes may be overrepresented among individuals with asthma and may have poorer lung function than non-carriers. Carriers of a single CF mutation have a higher prevalence of chronic rhinosinusitis than the general population. Approximately 50% of cystic fibrosis cases in Europe are due to homozygous ΔF508 mutations (this varies widely by region), while

639-453: A single copy of mutant CFTR are resistant to diarrhea caused by cholera toxin. The most common mutations that cause cystic fibrosis and pancreatic insufficiency in humans are: DeltaF508 ( ΔF508 ), full name CFTRΔF508 or F508del-CFTR ( rs113993960 ), is a specific mutation within the CFTR gene involving deletion of three nucleotides spanning codons for amino acid positions 507 and 508 of

710-647: A type organic salts exhibiting mesophases (i.e. a state of matter intermediate between liquid and solid), in which mobile ions are orientationally or rotationally disordered while their centers are located at the ordered sites in the crystal structure. They have various forms of disorder due to one or more solid–solid phase transitions below the melting point and have therefore plastic properties and good mechanical flexibility as well as an improved electrode-electrolyte interfacial contact. In particular, protic organic ionic plastic crystals (POIPCs), which are solid protic organic salts formed by proton transfer from

781-414: A type of highly conductive non-aqueous electrolytes and thus have found more and more applications in fuel cells and batteries. An electrolyte in a solution may be described as "concentrated" if it has a high concentration of ions, or "dilute" if it has a low concentration. If a high proportion of the solute dissociates to form free ions, the electrolyte is strong; if most of the solute does not dissociate,

SECTION 10

#1733086192225

852-406: A variety of substrates in eukaryotes. ABC transporters have evolved to transduce the free energy of ATP hydrolysis to the uphill movement of substrates across the cell membrane. They have two main conformations, one where the cargo binding site is facing the cytosol or inward facing (ATP free), and one where it is outward facing (ATP bound). ATP binds to each nucleotide-binding domain, which results in

923-422: Is a substance that conducts electricity through the movement of ions , but not through the movement of electrons . This includes most soluble salts , acids , and bases , dissolved in a polar solvent like water. Upon dissolving, the substance separates into cations and anions , which disperse uniformly throughout the solvent. Solid-state electrolytes also exist. In medicine and sometimes in chemistry,

994-455: Is an ion channel that evolved as a 'broken' ABC transporter that leaks when in the open conformation . CFTRs consist of five domains including two trans-membrane domains, each linked to a nucleotide-binding domain. CFTR also contains another domain called the regulatory domain. Other members of the ABC transporter superfamily are involved in the uptake of nutrients in prokaryotes, or in the export of

1065-424: Is approximately 189 kb in length, with 27 exons and 26 introns . CFTR is a glycoprotein and is found on the surface of many epithelial cells in the body. CFTR consists of five domains, which include two transmembrane or membrane-spanning domains, two nucleotide-binding domains and a regulatory domain. The transmembrane domains are each connected to a nucleotide binding domain (NBD) in the cytoplasm. The first NBD

1136-436: Is complicated due to a large number of disease-causing mutations. Ideally, a library of cell lines and cell-based assays corresponding to all mutants is required to screen for broadly-active drug candidates. Cell engineering methods including fluorogenic oligonucleotide signaling probes may be used to detect and isolate clonal cell lines for each mutant. Mutations consist of replacements, duplications, deletions or shortenings in

1207-451: Is connected to the second transmembrane domain by a regulatory "R" domain that is a unique feature of CFTR, not present in other ABC transporters which carries 19 predicted sites for protein kinase A(PKA). Six of these have been reported to be phosphorylated in vivo. The ion channel only opens when its R-domain has been phosphorylated by PKA and ATP is bound at the NBDs. Phosphorylation displaces

1278-801: Is coupled to transition to an outward-facing conformation in which an open transmembrane pathway for anions is formed. Subsequent hydrolysis (at the canonical active site, site 2, including Walker motifs of NBD2) destabilizes the NBD dimer and favors return to the inward-facing conformation, in which the anion permeation pathway is closed off. Different CFTR mutations can lead to varying degrees of cystic fibrosis severity. Common symptoms include chronic lung infections, pancreatic insufficiency, and high sweat chloride levels. Mutation-specific therapies, such as CFTR modulators, have been developed to address these specific genetic defects. Cystic fibrosis transmembrane conductance regulator has been shown to interact with: It

1349-498: Is encoded by the CFTR gene . Geneticist Lap-Chee Tsui and his team identified the CFTR gene in 1989 as the gene linked with CF ( cystic fibrosis ). The CFTR gene codes for an ABC transporter -class ion channel protein that conducts chloride and bicarbonate ions across epithelial cell membranes . Mutations of the CFTR gene affecting anion channel function lead to dysregulation of epithelial lining fluid (mucus) transport in

1420-449: Is estimated that 20–30% of all genes in most genomes encode for membrane proteins. For instance, about 1000 of the ~4200 proteins of E. coli are thought to be membrane proteins, 600 of which have been experimentally verified to be membrane resident. In humans, current thinking suggests that fully 30% of the genome encodes membrane proteins. Membrane proteins are the targets of over 50% of all modern medicinal drugs . Among

1491-418: Is important in the treatment of anorexia and bulimia . In science, electrolytes are one of the main components of electrochemical cells . In clinical medicine , mentions of electrolytes usually refer metonymically to the ions, and (especially) to their concentrations (in blood, serum, urine, or other fluids). Thus, mentions of electrolyte levels usually refer to the various ion concentrations, not to

SECTION 20

#1733086192225

1562-525: Is inhibited by the anti-diarrhoea drug crofelemer . CFTR has been a drug target in efforts to find treatments for related conditions. Ivacaftor (trade name Kalydeco, developed as VX-770) is a drug approved by the FDA in 2012 for people with cystic fibrosis who have specific CFTR mutations. Ivacaftor was developed by Vertex Pharmaceuticals in conjunction with the Cystic Fibrosis Foundation and

1633-416: Is located along the entire length of the cilia. In sweat glands , defective CFTR results in reduced transport of sodium chloride and sodium thiocyanate in the resorptive duct and therefore saltier sweat. This is the basis of a clinically important sweat test for cystic fibrosis often used diagnostically with genetic screening. The gene that encodes the human CFTR protein is found on chromosome 7 , on

1704-514: Is maintained by oral, or in emergencies, intravenous (IV) intake of electrolyte-containing substances, and is regulated by hormones , in general with the kidneys flushing out excess levels. In humans, electrolyte homeostasis is regulated by hormones such as antidiuretic hormones , aldosterone and parathyroid hormones . Serious electrolyte disturbances , such as dehydration and overhydration , may lead to cardiac and neurological complications and, unless they are rapidly resolved, will result in

1775-448: Is most highly expressed by rare specialized cells called pulmonary ionocytes . In the skin, CFTR is strongly expressed in the sebaceous and eccrine sweat glands. In the eccrine glands, CFTR is located on the apical membrane of the epithelial cells that make up the duct of these sweat glands. Normally, the protein allows movement of chloride , bicarbonate and thiocyanate ions (with a negative charge) out of an epithelial cell into

1846-443: Is required. In 2021, researchers have found that electrolyte can "substantially facilitate electrochemical corrosion studies in less conductive media". In physiology , the primary ions of electrolytes are sodium (Na ), potassium (K ), calcium (Ca ), magnesium (Mg ), chloride (Cl ), hydrogen phosphate (HPO 4 ), and hydrogen carbonate (HCO 3 ). The electric charge symbols of plus (+) and minus (−) indicate that

1917-400: Is shuttled to the cell membrane, where it becomes a transmembrane protein that forms aqueous channels allowing the flow of chloride and bicarbonate ions out of cells; it also simultaneously inhibits the uptake of sodium ions by another channel protein. Both of these functions help to maintain an ion gradient that causes osmosis to draw water out of the cells. The ΔF508 mutation leads to

1988-405: Is sufficient to produce mild lung abnormalities even in the absence of infection. The CFTR gene is located on the long arm of chromosome 7, at position q31.2, and ultimately codes for a sequence of 1,480 amino acids. Normally, the three DNA base pairs A-T-C (paired with T-A-G on the opposite strand) at the gene's 507th position form the template for the mRNA codon A-U-C for isoleucine , while

2059-511: Is the specific gravity test to determine the occurrence of an electrolyte imbalance . According to a study paid for by the Gatorade Sports Science Institute , electrolyte drinks containing sodium and potassium salts replenish the body's water and electrolyte concentrations after dehydration caused by exercise , excessive alcohol consumption , diaphoresis (heavy sweating), diarrhea, vomiting, intoxication or starvation;

2130-638: Is the first drug that treats the underlying cause rather than the symptoms of the disease. Called "the most important new drug of 2012", and "a wonder drug" it is one of the most expensive drugs, costing over US$ 300,000 per year, which has led to criticism of Vertex for the high cost. Membrane protein Membrane proteins are common, and medically important—about a third of all human proteins are membrane proteins, and these are targets for more than half of all drugs. Nonetheless, compared to other classes of proteins, determining membrane protein structures remains

2201-481: The CFTR gene. These mutations might be heterozygous, meaning they include two different mutations, and homozygous, meaning they involve the same mutation. Delta F508 is the most common mutation, accounting for more than 70% of all mutations. Those who are homozygous for Delta F508 are commonly affected by pancreatic insufficiency. The CFTR gene has been used in animals as a nuclear DNA phylogenetic marker. Large genomic sequences of this gene have been used to explore

Cystic fibrosis transmembrane conductance regulator - Misplaced Pages Continue

2272-492: The CFTR gene. This may result in proteins that may not function, work less effectively, are more quickly degraded, or are present in inadequate numbers. It has been hypothesized that mutations in the CFTR gene may confer a selective advantage to heterozygous individuals. Cells expressing a mutant form of the CFTR protein are resistant to invasion by the Salmonella typhi bacterium, the agent of typhoid fever , and mice carrying

2343-478: The lipid bilayer or to integral proteins by a combination of hydrophobic , electrostatic , and other non-covalent interactions. Peripheral proteins dissociate following treatment with a polar reagent, such as a solution with an elevated pH or high salt concentrations. Integral and peripheral proteins may be post-translationally modified, with added fatty acid , diacylglycerol or prenyl chains, or GPI (glycosylphosphatidylinositol), which may be anchored in

2414-427: The phylogeny of the major groups of mammals , and confirmed the grouping of placental orders into four major clades: Xenarthra , Afrotheria , Laurasiatheria , and Euarchonta plus Glires . Nearly 1000 cystic fibrosis-causing mutations have been described. The most common mutation, DeltaF508 (ΔF508) primarily known as a processing mutation which results from a deletion (Δ) of three nucleotides which results in

2485-720: The 1903 Nobel Prize in Chemistry. Arrhenius's explanation was that in forming a solution, the salt dissociates into charged particles, to which Michael Faraday (1791-1867) had given the name " ions " many years earlier. Faraday's belief had been that ions were produced in the process of electrolysis . Arrhenius proposed that, even in the absence of an electric current, solutions of salts contained ions. He thus proposed that chemical reactions in solution were reactions between ions. Shortly after Arrhenius's hypothesis of ions, Franz Hofmeister and Siegmund Lewith found that different ion types displayed different effects on such things as

2556-467: The Airway Surface Liquid and mucus . Positively charged sodium ions follow passively, increasing the total electrolyte concentration in the mucus, resulting in the movement of water out of the cell via osmosis . In epithelial cells with motile cilia lining the bronchus and the oviduct, CFTR is located on the apical cell membrane but not on cilia. In contrast, ENaC (Epithelial sodium channel)

2627-454: The CFTR gene on chromosome 7, which ultimately results in the loss of a single codon for the amino acid phenylalanine (F). A person with the CFTRΔF508 mutation will produce an abnormal CFTR protein that lacks this phenylalanine residue and which cannot fold properly. Most of this mutated protein does not escape the endoplasmic reticulum for further processing. The small amounts that reach

2698-449: The allele frequency of ΔF508 is about 70%. The remaining cases are caused by over 1,500 other mutations, including R117H, 1717-1G>A, and 2789+56G>A. These mutations, when combined with each other or even a single copy of ΔF508, may cause CF symptoms. The genotype is not strongly correlated with severity of the CF, though specific symptoms have been linked to certain mutations. The CFTR gene

2769-524: The anode. The ions in the electrolyte neutralize these charges, enabling the electrons to keep flowing and the reactions to continue. For example, in a solution of ordinary table salt (sodium chloride, NaCl) in water, the cathode reaction will be and hydrogen gas will bubble up; the anode reaction is and chlorine gas will be liberated into solution where it reacts with the sodium and hydroxyl ions to produce sodium hypochlorite - household bleach . The positively charged sodium ions Na will react toward

2840-552: The body. Muscles and neurons are activated by electrolyte activity between the extracellular fluid or interstitial fluid , and intracellular fluid . Electrolytes may enter or leave the cell membrane through specialized protein structures embedded in the plasma membrane called " ion channels ". For example, muscle contraction is dependent upon the presence of calcium (Ca ), sodium (Na ), and potassium (K ). Without sufficient levels of these key electrolytes, muscle weakness or severe muscle contractions may occur. Electrolyte balance

2911-495: The cathode, neutralizing the negative charge of OH there, and the negatively charged hydroxide ions OH will react toward the anode, neutralizing the positive charge of Na there. Without the ions from the electrolyte, the charges around the electrode would slow down continued electron flow; diffusion of H and OH through water to the other electrode takes longer than movement of the much more prevalent salt ions. Electrolytes dissociate in water because water molecules are dipoles and

Cystic fibrosis transmembrane conductance regulator - Misplaced Pages Continue

2982-524: The code for a protein structure. CFTR functions as phosphorylation and ATP - gated anion channel , increasing the conductance for certain anions (e.g. Cl) to flow down their electrochemical gradient . ATP-driven conformational changes in CFTR open and close a gate to allow the transmembrane flow of anions down their electrochemical gradient . This in contrast to other ABC proteins , in which ATP-driven conformational changes fuel uphill substrate transport across cellular membranes. Essentially, CFTR

3053-512: The dipoles orient in an energetically favorable manner to solvate the ions. In other systems, the electrode reactions can involve the metals of the electrodes as well as the ions of the electrolyte. Electrolytic conductors are used in electronic devices where the chemical reaction at a metal-electrolyte interface yields useful effects. Solid electrolytes can be mostly divided into four groups described below. Gel electrolytes – closely resemble liquid electrolytes. In essence, they are liquids in

3124-441: The disordered R domain from positions preventing NBD dimerization and opening. The amino-terminus is part of the lasso motif which anchors into the cell membrane. The carboxyl terminal of the protein is anchored to the cytoskeleton by a PDZ -interacting domain. The CFTR gene is made up of 27 exons that encode its gene makeup and is found on the long (q) arm of chromosome 7 at locus 31.2. Exons are DNA fragments that provide

3195-470: The dissociation reaction: It is also possible for substances to react with water, producing ions. For example, carbon dioxide gas dissolves in water to produce a solution that contains hydronium , carbonate , and hydrogen carbonate ions. Molten salts can also be electrolytes as, for example, when sodium chloride is molten, the liquid conducts electricity. In particular, ionic liquids, which are molten salts with melting points below 100 °C, are

3266-399: The electrolyte is weak. The properties of electrolytes may be exploited using electrolysis to extract constituent elements and compounds contained within the solution. Alkaline earth metals form hydroxides that are strong electrolytes with limited solubility in water, due to the strong attraction between their constituent ions. This limits their application to situations where high solubility

3337-445: The extracellular space, and an associated cascade of effects on various parts of the body. These effects include: thicker mucous membranes in the epithelia of afflicted organs; obstruction of narrow respiratory airways as a result of thicker mucus and inhibition of the free movement of muco cilia; congenital absence of the vas deferens due to increased mucus thickness during fetal development; pancreatic insufficiency due to blockage of

3408-417: The fluid volumes. The word electrolyte derives from Ancient Greek ήλεκτρο- ( ēlectro -), prefix originally meaning amber but in modern contexts related to electricity, and λυτός ( lytos ), meaning "able to be untied or loosened". In his 1884 dissertation, Svante Arrhenius put forth his explanation of solid crystalline salts disassociating into paired charged particles when dissolved, for which he won

3479-830: The human diseases in which membrane proteins have been implicated are heart disease , Alzheimer's and cystic fibrosis . Although membrane proteins play an important role in all organisms, their purification has historically, and continues to be, a huge challenge for protein scientists. In 2008, 150 unique structures of membrane proteins were available, and by 2019 only 50 human membrane proteins had had their structures elucidated. In contrast, approximately 25% of all proteins are membrane proteins. Their hydrophobic surfaces make structural and especially functional characterization difficult. Detergents can be used to render membrane proteins water-soluble , but these can also alter protein structure and function. Making membrane proteins water-soluble can also be achieved through engineering

3550-509: The lipid bilayer. Polypeptide toxins and many antibacterial peptides , such as colicins or hemolysins , and certain proteins involved in apoptosis , are sometimes considered a separate category. These proteins are water-soluble but can undergo significant conformational changes , form oligomeric complexes and associate irreversibly or reversibly with the lipid bilayer . Membrane proteins, like soluble globular proteins , fibrous proteins , and disordered proteins , are common. It

3621-415: The localization of hydrophobic amino acid sequences. Integral membrane proteins are permanently attached to the membrane. Such proteins can be separated from the biological membranes only using detergents , nonpolar solvents , or sometimes denaturing agents. They can be classified according to their relationship with the bilayer : Peripheral membrane proteins are temporarily attached either to

SECTION 50

#1733086192225

3692-441: The long arm at position q31.2. from base pair 116,907,253 to base pair 117,095,955. CFTR orthologs occur in the jawed vertebrates . Each individual inherits two copies of the CFTR (cystic fibrosis transmembrane conductance regulator) gene. However, some of the inherited copies have been altered. So far, the CFTR gene has been associated with over 700 distinct mutations. An individual with CF inherits two defective copies of

3763-526: The lung, pancreas and other organs, resulting in cystic fibrosis . Complications include thickened mucus in the lungs with frequent respiratory infections , and pancreatic insufficiency giving rise to malnutrition and diabetes . These conditions lead to chronic disability and reduced life expectancy. In male patients, the progressive obstruction and destruction of the developing vas deferens (spermatic cord) and epididymis appear to result from abnormal intraluminal secretions, causing congenital absence of

3834-406: The maintenance of precise osmotic gradients of electrolytes is important. Such gradients affect and regulate the hydration of the body as well as blood pH , and are critical for nerve and muscle function. Various mechanisms exist in living species that keep the concentrations of different electrolytes under tight control. Both muscle tissue and neurons are considered electric tissues of

3905-550: The melt acquires the capacity to conduct electricity. Sodium , potassium , chloride , calcium , magnesium , and phosphate in a liquid phase are examples of electrolytes. In medicine, electrolyte replacement is needed when a person has prolonged vomiting or diarrhea , and as a response to sweating due to strenuous athletic activity. Commercial electrolyte solutions are available, particularly for sick children (such as oral rehydration solution, Suero Oral , or Pedialyte ) and athletes ( sports drinks ). Electrolyte monitoring

3976-505: The misfolding of CFTR and its eventual degradation in the ER . In organisms with two complements of the mutation, the protein is almost entirely absent from the cell membrane, and these critical ion transport functions are not performed. Having a homozygous pair of genes with the ΔF508 mutation prevents the CFTR protein from assuming its normal position in the cell membrane. This causes increased water retention in cells, corresponding dehydration of

4047-571: The mutation's net effect is equivalent to a deletion ("Δ") of the sequence resulting in the codon for phenylalanine at position 508. ΔF508 is present on at least one copy of chromosome 7 in approximately one in 30 Caucasians . Presence of the mutation on both copies causes the autosomal recessive disease cystic fibrosis. Scientists have estimated that the original mutation occurred over 52,000 years ago in Northern Europe though cystic fibrosis patients of other ethnicities are also known to harbor

4118-523: The mutation. The young allele age may be a consequence of past selection. One hypothesis as to why the otherwise detrimental mutation has been maintained by natural selection is that a single copy may present a positive effect by reducing water loss during cholera , though the introduction of pathogenic Vibrio cholerae into Europe did not occur until the late 18th century. Another theory posits that CF carriers (heterozygotes for ΔF508) are more resistant to typhoid fever , since CFTR has been shown to act as

4189-585: The pancreatic duct with mucus; and increased risk of respiratory infection due to build-up of thick, nutrient-rich mucus where bacteria thrive. These are the symptoms of cystic fibrosis , a genetic disorder; however, ΔF508 is not the only mutation that causes this disorder. Being a heterozygous carrier (having a single copy of ΔF508) results in decreased water loss during diarrhea because malfunctioning or absent CFTR proteins cannot maintain stable ion gradients across cell membranes. Typical nucleotide-binding-up of both Cl and Na ions inside affected cells, creating

4260-417: The plasma membrane are destabilized and the anion channel opens infrequently. Having two copies of this mutation (one inherited from each parent) is by far the most common cause of cystic fibrosis (CF), responsible for nearly two-thirds of mutations worldwide. The CFTR protein is largely expressed in cells of the pancreas, intestinal and respiratory epithelia, and all exocrine glands. When properly folded, it

4331-462: The protein sequence, replacing selected hydrophobic amino acids with hydrophilic ones, taking great care to maintain secondary structure while revising overall charge. Affinity chromatography is one of the best solutions for purification of membrane proteins. The polyhistidine-tag is a commonly used tag for membrane protein purification, and the alternative rho1D4 tag has also been successfully used. Electrolyte An electrolyte

SECTION 60

#1733086192225

4402-476: The solid medium. Usually it is a relatively high- dielectric constant polymer ( PEO , PMMA , PAN , polyphosphazenes , siloxanes , etc.) and a salt with low lattice energy . In order to increase the mechanical strength and conductivity of such electrolytes, very often composites are made, and inert ceramic phase is introduced. There are two major classes of such electrolytes: polymer-in-ceramic, and ceramic-in-polymer. Organic ionic plastic crystals – are

4473-507: The solubility of proteins. A consistent ordering of these different ions on the magnitude of their effect arises consistently in many other systems as well. This has since become known as the Hofmeister series . While the origins of these effects are not abundantly clear and have been debated throughout the past century, it has been suggested that the charge density of these ions is important and might actually have explanations originating from

4544-464: The solution amounts to a current. Some gases, such as hydrogen chloride (HCl), under conditions of high temperature or low pressure can also function as electrolytes. Electrolyte solutions can also result from the dissolution of some biological (e.g., DNA , polypeptides ) or synthetic polymers (e.g., polystyrene sulfonate ), termed " polyelectrolytes ", which contain charged functional groups . A substance that dissociates into ions in solution or in

4615-714: The study says that athletes exercising in extreme conditions (for three or more hours continuously, e.g. a marathon or triathlon ) who do not consume electrolytes risk dehydration (or hyponatremia ). A home-made electrolyte drink can be made by using water, sugar and salt in precise proportions . It is important to include glucose (sugar) to utilise the co-transport mechanism of sodium and glucose. Commercial preparations are also available for both human and veterinary use. Electrolytes are commonly found in fruit juices , sports drinks, milk, nuts, and many fruits and vegetables (whole or in juice form) (e.g., potatoes, avocados ). When electrodes are placed in an electrolyte and

4686-562: The subsequent NBD dimerization, leading to the rearrangement of the transmembrane helices. This changes the accessibility of the cargo binding site from an inward-facing position to an outward facing one. ATP binding, and the hydrolysis that follows, drives the alternative exposure of the cargo binding site, ensuring a unidirectional transport of cargo against an electrochemical gradient . In CFTR, alternating between an inward-facing conformation to an outward-facing one results in channel gating. In particular, NBD dimerization (favored by ATP binding)

4757-463: The substance is ionic in nature and has an imbalanced distribution of electrons, the result of chemical dissociation . Sodium is the main electrolyte found in extracellular fluid and potassium is the main intracellular electrolyte; both are involved in fluid balance and blood pressure control. All known multicellular lifeforms require a subtle and complex electrolyte balance between the intracellular and extracellular environments. In particular,

4828-404: The term electrolyte refers to the substance that is dissolved. Electrically, such a solution is neutral. If an electric potential is applied to such a solution, the cations of the solution are drawn to the electrode that has an abundance of electrons , while the anions are drawn to the electrode that has a deficit of electrons. The movement of anions and cations in opposite directions within

4899-557: The three DNA base pairs T-T-T (paired with A-A-A) at the adjacent 508th position form the template for the codon U-U-U for phenylalanine . The ΔF508 mutation is a deletion of the C-G pair from position 507 along with the first two T-A pairs from position 508, leaving the DNA sequence A-T-T (paired with T-A-A) at position 507, which is transcribed into the mRNA codon A-U-U. Since A-U-U also codes for isoleucine, position 507's amino acid does not change, and

4970-401: The vas deferens and male infertility, and found associated with an imbalance of fatty acids . The CFTR is found in the epithelial cells of many organs including the lung , liver , pancreas , digestive tract, and the female reproductive tract and male reproductive tract including the testis, Sertoli cells, spermatozoa. epididymis, and the vas deferens. In the airways of the lung, CFTR

5041-453: The work of Charles-Augustin de Coulomb over 200 years ago. Electrolyte solutions are normally formed when salt is placed into a solvent such as water and the individual components dissociate due to the thermodynamic interactions between solvent and solute molecules, in a process called " solvation ". For example, when table salt ( sodium chloride ), NaCl, is placed in water, the salt (a solid) dissolves into its component ions, according to

#224775