Target type: biologicalprocess
The process of binding or confining calcium ions such that they are separated from other components of a biological system. [GOC:ai]
Calcium sequestration is a crucial biological process that involves the removal and storage of calcium ions (Ca2+) from the cytosol, the fluid inside cells. This process is essential for maintaining cellular homeostasis and regulating various cellular functions, including muscle contraction, neurotransmission, and cell signaling.
**Mechanisms of Calcium Sequestration:**
1. **Active Transport:** Calcium pumps, specifically calcium ATPases, use energy derived from ATP hydrolysis to actively transport Ca2+ ions across cellular membranes against their concentration gradient. This process results in the accumulation of Ca2+ in intracellular compartments, like the sarcoplasmic reticulum (SR) in muscle cells or the endoplasmic reticulum (ER) in other cells.
2. **Calcium Binding Proteins:** Proteins like calmodulin, troponin C, and parvalbumin have a high affinity for Ca2+ ions. They bind to Ca2+ and sequester it within the cytosol, effectively reducing the free Ca2+ concentration.
**Key Locations for Calcium Sequestration:**
- **Sarcoplasmic Reticulum (SR) in Muscle Cells:** The SR is a specialized organelle that stores large amounts of Ca2+. During muscle contraction, Ca2+ is released from the SR into the cytosol, triggering the interaction of actin and myosin filaments. After contraction, the Ca2+ is actively pumped back into the SR, allowing the muscle to relax.
- **Endoplasmic Reticulum (ER):** The ER serves as a major calcium storage site in most cells. Calcium pumps in the ER membrane actively transport Ca2+ from the cytosol into the ER lumen, where it is stored bound to proteins.
- **Mitochondria:** Mitochondria also play a role in Ca2+ sequestration, although their capacity is typically lower than that of the SR or ER. They can buffer cytosolic Ca2+ levels, but their primary function is in energy production through oxidative phosphorylation.
**Regulation of Calcium Sequestration:**
- **Hormones and Neurotransmitters:** Hormones like epinephrine and neurotransmitters like acetylcholine can trigger the release of Ca2+ from intracellular stores, initiating various cellular responses.
- **Intracellular Signaling Pathways:** Changes in cellular conditions, such as pH or phosphorylation, can affect the activity of calcium pumps and other proteins involved in Ca2+ sequestration.
**Consequences of Calcium Sequestration Dysregulation:**
- **Muscle Weakness and Fatigue:** Inadequate Ca2+ sequestration in muscle cells can lead to impaired muscle function and fatigue.
- **Neurological Disorders:** Dysregulation of Ca2+ homeostasis in neurons can contribute to conditions like epilepsy, Alzheimer's disease, and Parkinson's disease.
- **Cardiac Arrhythmias:** Abnormal Ca2+ handling in heart muscle cells can disrupt heart rhythm and lead to arrhythmias.
In summary, calcium sequestration is a vital process that plays a critical role in maintaining cellular function and regulating diverse physiological processes. Its precise regulation is crucial for normal cellular activity, and any disruption in this process can have significant consequences for health.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Presenilin-1 | A presenilin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49768] | Homo sapiens (human) |
| Endoplasmin | An endoplasmin that is encoded in the genome of human. [PRO:DAN] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| tocopheroxy radical | tocopheroxy radical: RN given refers to radical ion (1+), (2R-(2R*(4R*,8R*)))-isomer; RN for cpd without isomeric designation not available 12/90 | tocopherol | |
| 7-amino-4-chloro-3-methoxy-2-benzopyran-1-one | isocoumarins | ||
| adenosine diphosphate | Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. | adenosine 5'-phosphate; purine ribonucleoside 5'-diphosphate | fundamental metabolite; human metabolite |
| 2-chloroadenosine | 5-chloroformycin A: structure given in first source | purine nucleoside | |
| adenosine | quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit | adenosines; purines D-ribonucleoside | analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent |
| tarenflurbil | tarenflurbil: R-enantiomer of flurbiprofen but not a COX inhibitor; modulates NF-kB, gamma-secretase, amyloid beta-protein; | flurbiprofen | |
| cholanic acid | 5beta-cholanic acids; cholanic acid | ||
| adenosine-5'-carboxylic acid | purine nucleoside | ||
| adenosine 5'-carboxamide | adenosine 5'-carboxamide: structure | ||
| 5'-n-methylcarboxamideadenosine | 5'-N-methylcarboxamideadenosine: RN given refers to (beta-D)-isomer | ||
| n-methyladenosine | N-methyladenosine: is a inhibitor of cell differentiation N(6)-methyladenosine : A methyladenosine compound with one methyl group attached to N(6) of the adenine nucleobase. | methyladenosine | |
| ethyl adenosine-5'-carboxylate | ethyl adenosine-5'-carboxylate: potent vasoactive substance; RN given refers to parent cpd | ||
| adenosine 5'-phosphoramidate | adenosine 5'-phosphoramidate : The phosphoramadite analogue of AMP. | organic phosphoramidate | Mycoplasma genitalium metabolite |
| t0901317 | T0901317: an LXRalpha and LXRbeta agonist | ||
| adenosine-5'-(n-ethylcarboxamide) | Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity. N-ethyl-5'-carboxamidoadenosine : A derivative of adenosine in which the 5'-hydroxymethyl group is replaced by an N-ethylcarboxamido group. | adenosines; monocarboxylic acid amide | adenosine A1 receptor agonist; adenosine A2A receptor agonist; antineoplastic agent; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; vasodilator agent |
| adenosine-5'-(N-propyl)carboxamide | adenosine-5'-(N-propyl)carboxamide : A monocarboxylic acid amide that is the propyl amide of adenosine 5'-carboxylic acid. | adenosines; monocarboxylic acid amide | |
| n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester | DAPT : A dipeptide consisting of alanylphenylglycine derivatised as a 3,5-difluorophenylacetamide at the amino terminal and a tert-butyl ester at the carboxy terminal. A gamma-secretase inhibitor. | carboxylic ester; difluorobenzene; dipeptide; tert-butyl ester | EC 3.4.23.46 (memapsin 2) inhibitor |
| sulindac sulfide | sulindac sulfide : An aryl sulfide that is a metabolite of sulindac. A non-steroidal anti-inflammatory drug, which also has anticancer activity. sulindac sulfide: sulfated analog of indomethacin & inhibitor of prostaglandin synthesis in vitro; RN given refers to cpd without isomeric designation; structure given in first source | aryl sulfide; monocarboxylic acid; organofluorine compound | antineoplastic agent; apoptosis inducer; non-steroidal anti-inflammatory drug |
| l 685458 | L 685458: a gamma-secretase inhibitor; structure in first source L-685,458 : A peptide and carboxamide that is L-leucyl-L-phenylalaninamide, L-Leu-L-Phe-NH2, which has been acylated on the N-terminus by a Phe-Phe hydroxyethylene dipeptide isotere, 2R-benzyl-5S-tert-butoxycarbonylamino-4R-hydroxy-6-phenylhexanoic acid. Compounds based on the structure of L-685,458 are potent inhibitors of gamma-secretase, which mediates the final catalytic step that generates the amyloid beta-peptide (Abeta), which assembles into the neurotoxic aggregates in the brains of sufferers of Alzheimer's disease. | carbamate ester; monocarboxylic acid amide; peptide; secondary alcohol | EC 3.4.23.46 (memapsin 2) inhibitor; peptidomimetic |
| 1-aminoadenosine | 1-aminoadenosine: structure | ||
| 9h-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-n-(1-methylethyl)- | 9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-: an epichaperome (purine-scaffold) inhibitor; structure in first source | ||
| mk 0752 | |||
| 5'-amino-5'-deoxyadenosine | |||
| ly 450139 | peptide | ||
| chf 5074 | 1-(3',4'-dichloro-2-fluoro(1,1'-biphenyl)-4-yl)cyclopropanecarboxylic acid: a beta-amyloid(1-42) lowering agent; structure in first source | ||
| n-cyclopropyl adenosine-5'-carboxamide | |||
| ly 411575 | dibenzoazepine; difluorobenzene; lactam; secondary alcohol | EC 3.4.23.46 (memapsin 2) inhibitor | |
| 4-(2-((1r)-1-(((4-chlorophenyl)sulfonyl)-2,5-difluoroanilino)ethyl)-5-fluorophenyl)butanoic acid | sulfonamide | ||
| begacestat | |||
| ec 144 | EC 144: structure in first source | ||
| e 2012 | |||
| mrk 560 | MRK 560: a gamma-secretase inhibitor; MRK-560 is the (cis)-isomer; structure in first source | ||
| at 13387 | (2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanone: structure in first source onalespib : A member of the class of isoindoles that is isoindole in which the amino group has been acylated by a 2,4-dihydroxy-5-isopropylbenzoyl group and in which position 5 of the isoidole moiety has been substituted by a (4-methylpiperazin-1-yl)methyl group. A second-generation Hsp90 inhibitor. | benzamides; isoindoles; N-alkylpiperazine; resorcinols; tertiary carboxamide | antineoplastic agent; Hsp90 inhibitor |
| cnf 2024 | 2-aminopurines; aromatic ether; organochlorine compound; pyridines | antineoplastic agent; Hsp90 inhibitor | |
| snx 2112 | SNX 2112: an orally available small molecule Hsp90 inhibitor; structure in first source | ||
| 1, 3-di-(n-carboxybenzoyl-leucyl-leucyl)amino acetone | 1, 3-di-(N-carboxybenzoyl-leucyl-leucyl)amino acetone: structure in first source | ||
| pf 3084014 | nirogacestat : A member of the class of imidazoles that is 1H-imidazole substituted by a 1-[(2,2-dimethylpropyl)amino]-2-methylpropan-2-yl group at position 1 and a {N-[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-L-norvalyl}amino group at position 4. It is a gamma-secretase inhibitor whose hydrobromide salt is indicated for adult patients with progressing desmoid tumours who require systemic treatment. nirogacestat: an antineoplastic agent | ||
| bms 708163 | BMS 708163: structure in first source | oxadiazole; ring assembly | |
| ro 4929097 | dibenzoazepine; dicarboxylic acid diamide; lactam; organofluorine compound | EC 3.4.23.46 (memapsin 2) inhibitor | |
| jnj 40418677 | |||
| (r)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1h-pyrazolo(4,3-c)quinoline | (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo(4,3-c)quinoline: gamma secretase inhibitor; structure in first source | ||
| tas-116 | |||
| ver 52296 | luminespib : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-(2,4-dihydroxy-5-isopropylphenyl)-4-[4-(morpholin-4-ylmethyl)phenyl]-1,2-oxazole-3-carboxylic acid with the amino group of ethylamine. | aromatic amide; isoxazoles; monocarboxylic acid amide; morpholines; resorcinols | angiogenesis inhibitor; antineoplastic agent; Hsp90 inhibitor |
| sta 9090 | ring assembly; triazoles |