Target type: biologicalprocess
A homeostatic process involved in the maintenance of non-mineral tissue, by preventing mineralization of non-skeletal tissue. [PMID:21490328, PMID:30030150]
Inhibition of non-skeletal tissue mineralization is a complex biological process that involves a delicate balance of factors to prevent the formation of calcium phosphate crystals in tissues outside of bones and teeth. This process is essential for maintaining tissue integrity and functionality.
The primary mechanism of inhibition relies on the regulation of calcium and phosphate ions, which are the building blocks of hydroxyapatite, the mineral component of bones and teeth.
**1. Extracellular Matrix Regulation:** The extracellular matrix (ECM) surrounding cells plays a crucial role in preventing ectopic mineralization. Specific proteins in the ECM, such as **osteopontin, fibronectin, and collagen** bind to calcium and phosphate ions, sequestering them and preventing their interaction to form crystals. These proteins also provide a scaffold for cell adhesion and growth, further contributing to tissue homeostasis.
**2. Mineralization Inhibitors:** Several proteins specifically inhibit the formation of calcium phosphate crystals. **Pyrophosphate**, a small molecule, binds to hydroxyapatite nuclei, preventing their growth. **Anticalcin**, an enzyme found in several tissues, hydrolyzes inorganic pyrophosphate, maintaining its inhibitory activity.
**3. Cellular Mechanisms:** Cells themselves contribute to the inhibition of non-skeletal mineralization through various mechanisms:
* **Phosphatases** degrade phosphate groups, preventing their incorporation into hydroxyapatite.
* **Calcium-binding proteins** like **calbindin** regulate intracellular calcium levels, limiting its availability for mineralization.
* **Matrix metalloproteinases (MMPs)** degrade ECM components, preventing the formation of favorable nucleation sites for mineralization.
**4. Tissue-Specific Mechanisms:** Different tissues employ specialized mechanisms to prevent mineralization:
* **Blood vessels:** Endothelial cells produce **nitric oxide (NO)**, which inhibits the formation of calcium phosphate crystals and promotes vasodilation.
* **Kidney:** The kidney filters and excretes excess calcium and phosphate, maintaining their homeostasis in the blood.
* **Lungs:** Pulmonary surfactant prevents the deposition of calcium phosphate crystals in the alveoli, ensuring proper gas exchange.
**5. Dysregulation and Pathological Consequences:** When the delicate balance of these inhibitory factors is disrupted, abnormal mineralization can occur, leading to a variety of diseases:
* **Calcification of arteries** (atherosclerosis) can restrict blood flow and lead to heart disease.
* **Calcification of soft tissues** (calcinosis) can cause pain, stiffness, and impaired function.
* **Kidney stones** can form due to the precipitation of calcium phosphate in the renal tubules.
In conclusion, inhibition of non-skeletal tissue mineralization is a complex and tightly regulated process involving multiple cellular and extracellular factors. These factors act in concert to maintain tissue integrity and prevent the formation of ectopic mineral deposits. Disruptions in this intricate system can lead to various pathological conditions highlighting the vital importance of this biological process.'
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Protein | Definition | Taxonomy |
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Alkaline phosphatase, tissue-nonspecific isozyme | An alkaline phosphatase, tissue-nonspecific isozyme that is encoded in the genome of cow. [OMA:P09487, PRO:DNx] | Bos taurus (cattle) |
5'-nucleotidase | A 5-nucleotidase that is encoded in the genome of human. [PRO:WCB, UniProtKB:P21589] | Homo sapiens (human) |
Alkaline phosphatase, tissue-nonspecific isozyme | An alkaline phosphatase, tissue-nonspecific isozyme that is encoded in the genome of human. [PRO:DNx, UniProtKB:P05186] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
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theophylline | dimethylxanthine | adenosine receptor antagonist; anti-asthmatic drug; anti-inflammatory agent; bronchodilator agent; drug metabolite; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; fungal metabolite; human blood serum metabolite; immunomodulator; muscle relaxant; vasodilator agent | |
sulfamic acid | sulfamic acid : The simplest of the sulfamic acids consisting of a single sulfur atom covalently bound by single bonds to hydroxy and amino groups and by double bonds to two oxygen atoms. sulfamic acid: standard in alkalimetry; RN given refers to parent cpd; structure | sulfamic acids | |
adenosine monophosphate | Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. | adenosine 5'-phosphate; purine ribonucleoside 5'-monophosphate | adenosine A1 receptor agonist; cofactor; EC 3.1.3.1 (alkaline phosphatase) inhibitor; EC 3.1.3.11 (fructose-bisphosphatase) inhibitor; fundamental metabolite; micronutrient; nutraceutical |
leucine | leucine : A branched-chain amino acid that consists of glycine in which one of the hydrogens attached to the alpha-carbon is substituted by an isobutyl group. Leucine: An essential branched-chain amino acid important for hemoglobin formation. | amino acid zwitterion; L-alpha-amino acid; leucine; proteinogenic amino acid; pyruvate family amino acid | algal metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; plant metabolite; Saccharomyces cerevisiae metabolite |
phenylalanine | L-phenylalanine : The L-enantiomer of phenylalanine. phenylalanine : An aromatic amino acid that is alanine in which one of the methyl hydrogens is substituted by a phenyl group. Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE. | amino acid zwitterion; erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; phenylalanine; proteinogenic amino acid | algal metabolite; EC 3.1.3.1 (alkaline phosphatase) inhibitor; Escherichia coli metabolite; human xenobiotic metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
tryptophan | tryptophan : An alpha-amino acid that is alanine bearing an indol-3-yl substituent at position 3. Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals. | erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; L-alpha-amino acid zwitterion; proteinogenic amino acid; tryptophan; tryptophan zwitterion | antidepressant; Escherichia coli metabolite; human metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
1-naphthol-8-amino-3,6-disulfonic acid | 1-naphthol-8-amino-3,6-disulfonic acid: dye and found in industrial waste | ||
4-sulfanilic acid | 4-aminobenzenesulfonic acid : An aminobenzenesulfonic acid that is aniline sulfonated at the para-position. 4-sulfanilic acid: minor descriptor (75-82); online search SULFANILIC ACIDS; Index Medicus search BENZENESULFONATES | aminobenzenesulfonic acid | allergen; environmental contaminant; xenobiotic; xenobiotic metabolite |
homoarginine | L-homoarginine : An L-lysine derivative that is the L-enantiomer of homoarginine. | homoarginine; L-lysine derivative; non-proteinogenic L-alpha-amino acid | biomarker; EC 3.1.3.1 (alkaline phosphatase) inhibitor; human metabolite; rat metabolite; xenobiotic metabolite |
levamisole | levamisole : A 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole that has S configuration. It is used (generally as the monohydrochloride salt) to treat parasitic worm infections in pigs, sheep and cattle and was formerly used in humans as an adjuvant to chemotherapy for the treatment of various cancers. It is also widely used as an adulterant to coccaine. Levamisole: An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6) | 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole | antinematodal drug; antirheumatic drug; EC 3.1.3.1 (alkaline phosphatase) inhibitor; immunological adjuvant; immunomodulator |
levamisole hydrochloride | organic molecular entity | ||
1-(3,4-dihydroxyphenyl)-2-(1-imidazolyl)ethanone | aromatic ketone | ||
betulinic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | anti-HIV agent; anti-inflammatory agent; antimalarial; antineoplastic agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; plant metabolite | |
1,2,3,4,6-pentakis-O-galloyl-beta-D-glucose | 1,2,3,4,6-pentakis-O-galloyl-beta-D-glucose : A galloyl-beta-D-glucose compound having five galloyl groups in the 1-, 2-, 3-, 4- and 6-positions. pentagalloylglucose: pentahydroxy gallic acid ester of glucose; a phytogenic antineoplastic agent and antibacterial agent | gallate ester; galloyl beta-D-glucose | anti-inflammatory agent; antineoplastic agent; geroprotector; hepatoprotective agent; plant metabolite; radiation protective agent; radical scavenger |
betulin | betulin : A pentacyclic triterpenoid that is lupane having a double bond at position 20(29) as well as 3beta-hydroxy and 28-hydroxymethyl substituents. betulin: isolated from various white birch bark (BETULA) | diol; pentacyclic triterpenoid | analgesic; anti-inflammatory agent; antineoplastic agent; antiviral agent; metabolite |
adenosine 5'-methylenediphosphate | nucleoside diphosphate analogue | ||
Lup-20(29)-en-28-al, 3beta-hydroxy- | triterpenoid | ||
betulonic acid | betulonic acid: isolated from Rush javanica; strucure in first source | triterpenoid | anticoronaviral agent |
fludarabine | purine nucleoside | ||
1-(3,4-dihydroxyphenyl)-2-[(4,6-dimethyl-2-pyrimidinyl)thio]ethanone | aromatic ketone | ||
2,5-dimethoxy-n-(quinolin-3-yl)benzenesulfonamide | 2,5-dimethoxy-N-(quinolin-3-yl)benzenesulfonamide: a tissue-nonspecific alkaline phosphatase inhibitor; structure in first source | quinolines | |
ellagic acid | catechols; cyclic ketone; lactone; organic heterotetracyclic compound; polyphenol | antioxidant; EC 1.14.18.1 (tyrosinase) inhibitor; EC 2.3.1.5 (arylamine N-acetyltransferase) inhibitor; EC 2.4.1.1 (glycogen phosphorylase) inhibitor; EC 2.5.1.18 (glutathione transferase) inhibitor; EC 2.7.1.127 (inositol-trisphosphate 3-kinase) inhibitor; EC 2.7.1.151 (inositol-polyphosphate multikinase) inhibitor; EC 2.7.4.6 (nucleoside-diphosphate kinase) inhibitor; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; food additive; fungal metabolite; geroprotector; plant metabolite; skin lightening agent | |
3-nitrobenzaldehyde isonicotinoylhydrazone | 3-nitrobenzaldehyde isonicotinoylhydrazone: structure in first source | ||
23-hydroxybetulinic acid | 23-hydroxybetulinic acid: structure in first source | triterpenoid | metabolite |
salinazid | aromatic carboxylic acid; pyridinemonocarboxylic acid | ||
phthivazide |