Page last updated: 2024-10-24

intracellular pH elevation

Definition

Target type: biologicalprocess

Any process that increases the internal pH of a cell, measured by the concentration of the hydrogen ion. [GOC:ai]

Intracellular pH elevation, also known as intracellular alkalinization, is a critical process involved in various cellular functions. The pH of the intracellular environment is maintained within a narrow range, typically around 7.2, which is essential for optimal enzyme activity, protein folding, and signaling pathways.

Several mechanisms contribute to intracellular pH elevation:

1. **Na+/H+ exchanger (NHE):** This transmembrane protein utilizes the electrochemical gradient of sodium ions (Na+) to pump protons (H+) out of the cell, thus increasing intracellular pH. NHE activity is regulated by various factors, including intracellular pH itself, signaling pathways, and growth factors.

2. **Cl-/HCO3- exchanger (AE):** This exchanger facilitates the movement of chloride ions (Cl-) into the cell and bicarbonate ions (HCO3-) out of the cell, leading to intracellular alkalinization. AE activity is influenced by the concentration of intracellular chloride ions and bicarbonate ions.

3. **Carbonic anhydrase (CA):** This enzyme catalyzes the reversible hydration of carbon dioxide (CO2) to form bicarbonate ions (HCO3-), which can then be exchanged for chloride ions by the AE.

4. **Metabolic activity:** Cellular metabolism, such as glycolysis and oxidative phosphorylation, can generate protons as byproducts. To maintain intracellular pH, these protons are transported out of the cell through various mechanisms, including NHE and AE.

5. **Plasma membrane H+ pump:** This transporter directly extrudes protons out of the cell, contributing to pH elevation.

6. **Intracellular buffering systems:** Intracellular buffers, such as proteins, phosphates, and bicarbonate, can temporarily bind protons and minimize pH fluctuations.

Intracellular pH elevation is involved in various physiological processes:

* **Cell growth and proliferation:** Increased intracellular pH promotes cell growth and proliferation by activating signaling pathways involved in cell cycle progression.
* **Apoptosis (programmed cell death):** Elevated intracellular pH can trigger apoptotic pathways, contributing to the elimination of damaged or unwanted cells.
* **Signal transduction:** Changes in intracellular pH can activate or inhibit specific signaling pathways, regulating various cellular processes.
* **Immune response:** Intracellular pH plays a role in immune cell activation and cytokine production.

The regulation of intracellular pH is a complex process involving multiple pathways and factors. Disruptions in pH homeostasis can lead to various pathological conditions, including cancer, neurodegenerative diseases, and metabolic disorders.'
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Proteins (1)

ProteinDefinitionTaxonomy
Cystic fibrosis transmembrane conductance regulatorA cystic fibrosis transmembrane conductance regulator that is encoded in the genome of human. [PRO:CNA, UniProtKB:P13569]Homo sapiens (human)

Compounds (13)

CompoundDefinitionClassesRoles
glyburideglyburide : An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group.

Glyburide: An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide
monochlorobenzenes;
N-sulfonylurea
anti-arrhythmia drug;
EC 2.7.1.33 (pantothenate kinase) inhibitor;
EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor;
hypoglycemic agent
methyl anthranilatemethyl anthranilate : A benzoate ester that is the methyl ester of anthranilic acid.benzoate esterflavouring agent;
metabolite
telmisartantelmisartan : A member of the class of benzimidazoles used widely in the treatment of hypertension.

Telmisartan: A biphenyl compound and benzimidazole derivative that acts as an angiotensin II type 1 receptor antagonist. It is used in the management of HYPERTENSION.
benzimidazoles;
biphenyls;
carboxybiphenyl
angiotensin receptor antagonist;
antihypertensive agent;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor;
environmental contaminant;
xenobiotic
tadalafilbenzodioxoles;
pyrazinopyridoindole
EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor;
vasodilator agent
7-n-butyl-6-(4'-hydroxyphenyl)-5h-pyrrolo(2,3b)pyrazine
3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone: a cystic fibrosis transmembrane conductance regulator inhibitor; structure in first source
uccf-029organic heterotricyclic compound;
organooxygen compound
quercetin7-hydroxyflavonol;
pentahydroxyflavone
antibacterial agent;
antineoplastic agent;
antioxidant;
Aurora kinase inhibitor;
chelator;
EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor;
geroprotector;
phytoestrogen;
plant metabolite;
protein kinase inhibitor;
radical scavenger
apigeninChamomile: Common name for several daisy-like plants (MATRICARIA; TRIPLEUROSPERMUM; ANTHEMIS; CHAMAEMELUM) native to Europe and Western Asia, now naturalized in the United States and Australia.trihydroxyflavoneantineoplastic agent;
metabolite
rutinHydroxyethylrutoside: Monohydroxyethyl derivative of rutin. Peripheral circulation stimulant used in treatment of venous disorders.disaccharide derivative;
quercetin O-glucoside;
rutinoside;
tetrahydroxyflavone
antioxidant;
metabolite
genistein7-hydroxyisoflavonesantineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
geroprotector;
human urinary metabolite;
phytoestrogen;
plant metabolite;
tyrosine kinase inhibitor
vx-770ivacaftor : An aromatic amide obtained by formal condensation of the carboxy group of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid with the amino group of 5-amino-2,4-di-tert-butylphenol. Used for the treatment of cystic fibrosis.

ivacaftor: a CFTR potentiator; structure in first source
aromatic amide;
monocarboxylic acid amide;
phenols;
quinolone
CFTR potentiator;
orphan drug
lumacaftorlumacaftor : An aromatic amide obtained by formal condensation of the carboxy group of 1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropane-1-carboxylic acid with the aromatic amino group of 3-(6-amino-3-methylpyridin-2-yl)benzoic acid. Used for the treatment of cystic fibrosis.

lumacaftor: a corrector of CF transmembrane conductance regulator (CTFR); structure in first source
aromatic amide;
benzodioxoles;
benzoic acids;
cyclopropanes;
organofluorine compound;
pyridines
CFTR potentiator;
orphan drug