CIDeRplusGeneral Information:
| Id: | 9,377 |
| Diseases: |
Hypophosphatasia, adult
- [OMIM]
Hypophosphatasia, childhood - [OMIM] Hypophosphatasia, infantile - [OMIM] |
| Mammalia | |
| review | |
| Reference: | Rader BA(2017) Alkaline Phosphatase, an Unconventional Immune Protein Front Immunol 8: 897 [PMID: 28824625] |
Interaction Information:
| Comment | TNAP plays a role in multiple processes, including bone mineralization, vitamin B6 metabolism, and neurogenesis, is the genetic cause of hypophosphatasia, influences inflammation through regulation of purinergic signaling, and has been implicated in Alzheimer's disease. |
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Formal Description Interaction-ID: 99721 |
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| Comment | TNAP plays a role in multiple processes, including bone mineralization, vitamin B6 metabolism, and neurogenesis, is the genetic cause of hypophosphatasia, influences inflammation through regulation of purinergic signaling, and has been implicated in Alzheimer's disease. |
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Formal Description Interaction-ID: 100008 |
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| Comment | TNAP plays a role in multiple processes, including bone mineralization, vitamin B6 metabolism, and neurogenesis, is the genetic cause of hypophosphatasia, influences inflammation through regulation of purinergic signaling, and has been implicated in Alzheimer's disease. |
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Formal Description Interaction-ID: 100009 |
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| Comment | TNAP plays a role in multiple processes, including bone mineralization, vitamin B6 metabolism, and neurogenesis, is the genetic cause of hypophosphatasia, influences inflammation through regulation of purinergic signaling, and has been implicated in Alzheimer's disease. Extracellular ATP and ADP, through the binding of nucleotide receptors, act as signals inducing inflammation after an acute event such as necrosis induced by damage or infection that releases intracellular nucleotides. In contrast, degradation of extracellular ATP and ADP to AMP and adenine causes cessation of inflammatory signaling, and induction through adenine receptors of an antiinflammation response. TNAP has been implicated in protection against inflammation in multiple diseases and promotion of intestinal microbial populations through hydrolysis of extracellular ATP/ADP to AMP and adenosine. |
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Formal Description Interaction-ID: 100010 |
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| Comment | TNAP plays a role in multiple processes, including bone mineralization, vitamin B6 metabolism, and neurogenesis, is the genetic cause of hypophosphatasia, influences inflammation through regulation of purinergic signaling, and has been implicated in Alzheimer's disease. |
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Formal Description Interaction-ID: 100011 |
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| Comment | IAP regulates fatty acid absorption and has been implicated in the regulation of diet-induced obesity and metabolic syndrome. |
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Formal Description Interaction-ID: 100012 |
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| Comment | IAP and TNAP can dephosphorylate bacterial-derived lipopolysaccharide, and IAP has been identified as a potential regulator of the composition of the intestinal microbiome, an evolutionarily conserved function. |
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Formal Description Interaction-ID: 100013 |
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| Comment | IAP and TNAP can dephosphorylate bacterial-derived lipopolysaccharide, and IAP has been identified as a potential regulator of the composition of the intestinal microbiome, an evolutionarily conserved function. |
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Formal Description Interaction-ID: 100015 |
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| Comment | The most direct link between alkaline phosphatases (APs) and human disease is hypo-phosphatasia (HPP), a disease characterized by mutations in TNAP associated with decreased enzyme activity in specific organs. This decrease in AP activity results in variable symptoms that range from perinatal HPP that can result in still birth from profound skeletal hypomineralization, potentially lethal seizures in infantile HPP, to milder phenotypes such as bone fractures and periodontal disease in juvenile HPP and adult HPP. |
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Formal Description Interaction-ID: 100017 |
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| Comment | The most direct link between alkaline phosphatases (APs) and human disease is hypo-phosphatasia (HPP), a disease characterized by mutations in TNAP associated with decreased enzyme activity in specific organs. This decrease in AP activity results in variable symptoms that range from perinatal HPP that can result in still birth from profound skeletal hypomineralization, potentially lethal seizures in infantile HPP, to milder phenotypes such as bone fractures and periodontal disease in juvenile HPP and adult HPP. |
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Formal Description Interaction-ID: 100022 |
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| Comment | The most direct link between alkaline phosphatases (APs) and human disease is hypo-phosphatasia (HPP), a disease characterized by mutations in TNAP associated with decreased enzyme activity in specific organs. This decrease in AP activity results in variable symptoms that range from perinatal HPP that can result in still birth from profound skeletal hypomineralization, potentially lethal seizures in infantile HPP, to milder phenotypes such as bone fractures and periodontal disease in juvenile HPP and adult HPP. |
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Formal Description Interaction-ID: 100024 |
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| Comment | Tissue nonspecific alkaline phosphatase (TNAP) is anchored to the cell membranes of osteoblasts and chondrocytes and to matrix vesicles released by those cells, where it degrades PPi to Pi. PPi is an inhibitor of mineralization and regulation by TNAP controls propagation of extracellular mineralization of apatite crystals. TNAP deficiency increases the amount of inhibitory PPi thus decreasing extracellular mineralization, and humans with HPP show a loss of mineralization fronts. This has been recapitulated in a TNAP knockout mouse model for infantile HPP. The loss of mineralization results in various symptoms including softening of bone, bowing and spontaneous breakage of bones, rickets, and tooth (dentin/cementum/enamel) defects. |
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Formal Description Interaction-ID: 100028 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Tissue nonspecific alkaline phosphatase (TNAP) is anchored to the cell membranes of osteoblasts and chondrocytes and to matrix vesicles released by those cells, where it degrades PPi to Pi. PPi is an inhibitor of mineralization and regulation by TNAP controls propagation of extracellular mineralization of apatite crystals. TNAP deficiency increases the amount of inhibitory PPi thus decreasing extracellular mineralization, and humans with HPP show a loss of mineralization fronts. This has been recapitulated in a TNAP knockout mouse model for infantile HPP. The loss of mineralization results in various symptoms including softening of bone, bowing and spontaneous breakage of bones, rickets, and tooth (dentin/cementum/enamel) defects. |
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Formal Description Interaction-ID: 100029 |
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| Comment | Tissue nonspecific alkaline phosphatase (TNAP) is anchored to the cell membranes of osteoblasts and chondrocytes and to matrix vesicles released by those cells, where it degrades PPi to Pi. PPi is an inhibitor of mineralization and regulation by TNAP controls propagation of extracellular mineralization of apatite crystals. TNAP deficiency increases the amount of inhibitory PPi thus decreasing extracellular mineralization, and humans with HPP show a loss of mineralization fronts. This has been recapitulated in a TNAP knockout mouse model for infantile HPP. The loss of mineralization results in various symptoms including softening of bone, bowing and spontaneous breakage of bones, rickets, and tooth (dentin/cementum/enamel) defects. |
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Formal Description Interaction-ID: 100032 |
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| Drugbank entries | Show/Hide entries for Diphosphate |
| Comment | Pyridoxal-5-phosphate, the active form of vitamin B6, is elevated in the serum of HPP patients. Hydrolysis of PLP to pyridoxal (PL) by TNAP facilitates diffusion of PL across cell membranes, where it is then re-phosphorylated into PLP. PLP is a versatile cofactor for an estimated 4% of enzymatic reactions and is used by over 110 enzymes to produce or metabolize various molecules. PLP-dependent enzymes in the brain are responsible for the production of important neurochemicals including serotonin, dopamine, and gamma-aminobutyric acid. The decrease in PLP and resulting decrease in PLP-dependent metabolism in the brain in perinatal HPP patients has been implicated as the cause of neonatal seizures. |
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Formal Description Interaction-ID: 100036 |
disease Hypophosphatasia increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | Pyridoxal-5-phosphate, the active form of vitamin B6, is elevated in the serum of HPP patients. Hydrolysis of PLP to pyridoxal (PL) by TNAP facilitates diffusion of PL across cell membranes, where it is then re-phosphorylated into PLP. PLP is a versatile cofactor for an estimated 4% of enzymatic reactions and is used by over 110 enzymes to produce or metabolize various molecules. PLP-dependent enzymes in the brain are responsible for the production of important neurochemicals including serotonin, dopamine, and gamma-aminobutyric acid. The decrease in PLP and resulting decrease in PLP-dependent metabolism in the brain in perinatal HPP patients has been implicated as the cause of neonatal seizures. |
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Formal Description Interaction-ID: 100037 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Pyridoxal-5-phosphate, the active form of vitamin B6, is elevated in the serum of HPP patients. Hydrolysis of PLP to pyridoxal (PL) by TNAP facilitates diffusion of PL across cell membranes, where it is then re-phosphorylated into PLP. PLP is a versatile cofactor for an estimated 4% of enzymatic reactions and is used by over 110 enzymes to produce or metabolize various molecules. PLP-dependent enzymes in the brain are responsible for the production of important neurochemicals including serotonin, dopamine, and gamma-aminobutyric acid. The decrease in PLP and resulting decrease in PLP-dependent metabolism in the brain in perinatal HPP patients has been implicated as the cause of neonatal seizures. |
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Formal Description Interaction-ID: 100038 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Pyridoxal-5-phosphate, the active form of vitamin B6, is elevated in the serum of HPP patients. Hydrolysis of PLP to pyridoxal (PL) by TNAP facilitates diffusion of PL across cell membranes, where it is then re-phosphorylated into PLP. PLP is a versatile cofactor for an estimated 4% of enzymatic reactions and is used by over 110 enzymes to produce or metabolize various molecules. PLP-dependent enzymes in the brain are responsible for the production of important neurochemicals including serotonin, dopamine, and gamma-aminobutyric acid. The decrease in PLP and resulting decrease in PLP-dependent metabolism in the brain in perinatal HPP patients has been implicated as the cause of neonatal seizures. |
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Formal Description Interaction-ID: 100039 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Pyridoxal phosphate |
| Comment | Pyridoxal-5-phosphate, the active form of vitamin B6, is elevated in the serum of HPP patients. Hydrolysis of PLP to pyridoxal (PL) by TNAP facilitates diffusion of PL across cell membranes, where it is then re-phosphorylated into PLP. PLP is a versatile cofactor for an estimated 4% of enzymatic reactions and is used by over 110 enzymes to produce or metabolize various molecules. PLP-dependent enzymes in the brain are responsible for the production of important neurochemicals including serotonin, dopamine, and gamma-aminobutyric acid. The decrease in PLP and resulting decrease in PLP-dependent metabolism in the brain in perinatal HPP patients has been implicated as the cause of neonatal seizures. |
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Formal Description Interaction-ID: 100040 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Pyridoxal phosphate or Dopamine |
| Comment | Pyridoxal-5-phosphate, the active form of vitamin B6, is elevated in the serum of HPP patients. Hydrolysis of PLP to pyridoxal (PL) by TNAP facilitates diffusion of PL across cell membranes, where it is then re-phosphorylated into PLP. PLP is a versatile cofactor for an estimated 4% of enzymatic reactions and is used by over 110 enzymes to produce or metabolize various molecules. PLP-dependent enzymes in the brain are responsible for the production of important neurochemicals including serotonin, dopamine, and gamma-aminobutyric acid. The decrease in PLP and resulting decrease in PLP-dependent metabolism in the brain in perinatal HPP patients has been implicated as the cause of neonatal seizures. |
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Formal Description Interaction-ID: 100041 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Pyridoxal phosphate |
| Comment | TNAP upregulation in the vasculature contributes to medial vascular calcification causing vascular stiffening and eventually heart failure. |
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Formal Description Interaction-ID: 100042 |
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| Comment | Tissue nonspecific alkaline phosphatase (TNAP) is anchored to the cell membranes of osteoblasts and chondrocytes and to matrix vesicles released by those cells, where it degrades PPi to Pi. PPi is an inhibitor of mineralization and regulation by TNAP controls propagation of extracellular mineralization of apatite crystals. TNAP deficiency increases the amount of inhibitory PPi thus decreasing extracellular mineralization, and humans with HPP show a loss of mineralization fronts. This has been recapitulated in a TNAP knockout mouse model for infantile HPP. The loss of mineralization results in various symptoms including softening of bone, bowing and spontaneous breakage of bones, rickets, and tooth (dentin/cementum/enamel) defects. |
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Formal Description Interaction-ID: 100043 |
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| Drugbank entries | Show/Hide entries for |
| Comment | IAP has been shown to dephosphorylate (detoxify) the lipid A moiety of lipopolysaccharide (LPS), the outer lipid layer of the outer membrane of Gram-negative bacteria. In vertebrates, these phosphates are important for binding of LPS to the toll-like receptor 4/MD-2 innate immune receptor complex, initiation of NF-kappaB signaling, and immune response induction. Intestinal AP deficiency has been associated with inflammation in the human intestine and in the intestines of vertebrate models in which AP levels are decreased. Supplementation of IAP to animals where intestinal inflammation is induced directly or indirectly (with antibiotic use for example) reduces inflammation. In addition, a protective role has been ascribed to IAP in mouse models of necrotizing enterocolitis. This protective role may include IAP-dependent shaping and homeostasis of the microbiome. Along with direct regulation of intestinal homeostasis, IAPs and LPS detoxification have been implicated in other immune-related processes including prevention of bacterial translocation by endogenous or pharmacologically administered IAPs, and resolution of intestinal inflammation and tissue regeneration. |
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Formal Description Interaction-ID: 100044 |
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