CIDeRplusGeneral Information:
| Id: | 9,380 |
| Diseases: |
Hypophosphatasia, adult
- [OMIM]
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| Mammalia | |
| review | |
| Reference: | Orimo H(2016) Pathophysiology of hypophosphatasia and the potential role of asfotase alfa Ther Clin Risk Manag 12: 777-786 [PMID: 27274262] |
Interaction Information:
| Comment | Hypophosphatasia (HPP) is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. |
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Formal Description Interaction-ID: 99724 |
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| Comment | Hypophosphatasia (HPP) is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. The causative gene of the disease is the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP is expressed ubiquitously, and its physiological role is apparent in bone mineralization. |
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Formal Description Interaction-ID: 101963 |
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| Comment | To express enzymatic activity, TNAP needs two Zn2+, one Mg2+, and one Ca2+ ion as cofactors. |
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Formal Description Interaction-ID: 101965 |
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| Comment | To express enzymatic activity, TNAP needs two Zn2+, one Mg2+, and one Ca2+ ion as cofactors. |
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Formal Description Interaction-ID: 101966 |
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| Comment | To express enzymatic activity, TNAP needs two Zn2+, one Mg2+, and one Ca2+ ion as cofactors. |
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Formal Description Interaction-ID: 101968 |
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| Comment | TNAP is essential for tissue biomineralization. |
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Formal Description Interaction-ID: 101970 |
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| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101972 |
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| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101983 |
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| Drugbank entries | Show/Hide entries for PHOSPHO1 |
| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101986 |
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| Drugbank entries | Show/Hide entries for PHOSPHO1 |
| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101987 |
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| Drugbank entries | Show/Hide entries for PHOSPHO1 |
| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101988 |
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| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101989 |
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| Drugbank entries | Show/Hide entries for ANXA2 |
| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101990 |
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| Drugbank entries | Show/Hide entries for ANXA5 |
| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101991 |
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| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101992 |
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| Comment | TNAP is essential for tissue biomineralization. Mineralization takes place in two distinct processes. Hypertrophic chondrocytes, osteoblasts, and odontoblasts bud matrix vesicles when mineralization begins. Matrix vesicles are membrane-invested vesicles of 50‚Äď200 nm in diameter and are rich in annexins A2, A5, and A6, and in Ca2+-ATPase, TNAP, nucleotide pyrophosphate phosphodi-esterase 1 (NPP1, formerly known as PC-1), Pit1 (a sodium‚Äďphosphate [Na/Pi] cotransporter), and PHOSPHO1. The first step of the mineralization process occurs within the matrix vesicles, in which hydroxyapatite (Ca10(PO4)6(OH)2) crystals are formed. Phosphate is derived from membrane phospholipids, which are hydrolyzed by phospholipase C to produce phosphocholine and phosphoethanolamine. These phosphocompounds are hydrolyzed by PHOSPHO1, a cytosolic phosphatase that is abundant in the matrix vesicles, to yield inorganic phosphate (Pi). Another source of Pi in the matrix vesicles is Pi that is transported through the Na/Pi cotransporter Pit1 that is also abundant on the matrix vesicle membrane. Calcium is incorporated into the matrix vesicles through annexin Ca2+ channels that consist of annexins A2, A5, and A6. Developing hydroxyapatite crystals then penetrate the matrix vesicle membrane, are elongated in the extracellular space, and eventually deposit in the spaces between collagen fibrils to complete extracellular matrix mineralization. |
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Formal Description Interaction-ID: 101993 |
drug/chemical compound increases_quantity of drug/chemical compound Calcium hydroxyapatite |
| Comment | The concentration ratio of Pi to inorganic pyrophosphate (PPi) in the extracellular matrix is crucial in the second step of mineralization because PPi is an inhibitor of hydroxyapatite formation. Two mechanisms are used for PPi formation. PPi is formed in the extracellular matrix from ATP by the matrix vesicle membrane enzyme NPP1. PPi is also provided through the PPi transporter ANKH (a homologue of the mouse progressive ankylosis gene product) from the cytoplasm, in which PPi is routinely formed by cellular metabolism. ANKH is distributed onthe plasma membrane of hypertrophic chondrocytes and osteoblasts. TNAP on the membrane of the matrix vesicles hydrolyzes PPi and yields Pi, thereby reducing the levels of the PPi inhibitor and promoting hydroxyapatite formation. |
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Formal Description Interaction-ID: 101994 |
drug/chemical compound affects_quantity of drug/chemical compound Calcium hydroxyapatite |
| Drugbank entries | Show/Hide entries for Diphosphate |
| Comment | The concentration ratio of Pi to inorganic pyrophosphate (PPi) in the extracellular matrix is crucial in the second step of mineralization because PPi is an inhibitor of hydroxyapatite formation. Two mechanisms are used for PPi formation. PPi is formed in the extracellular matrix from ATP by the matrix vesicle membrane enzyme NPP1. PPi is also provided through the PPi transporter ANKH (a homologue of the mouse progressive ankylosis gene product) from the cytoplasm, in which PPi is routinely formed by cellular metabolism. ANKH is distributed onthe plasma membrane of hypertrophic chondrocytes and osteoblasts. TNAP on the membrane of the matrix vesicles hydrolyzes PPi and yields Pi, thereby reducing the levels of the PPi inhibitor and promoting hydroxyapatite formation. |
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Formal Description Interaction-ID: 101995 |
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| Drugbank entries | Show/Hide entries for ENPP1 or Diphosphate |
| Comment | The concentration ratio of Pi to inorganic pyrophosphate (PPi) in the extracellular matrix is crucial in the second step of mineralization because PPi is an inhibitor of hydroxyapatite formation. Two mechanisms are used for PPi formation. PPi is formed in the extracellular matrix from ATP by the matrix vesicle membrane enzyme NPP1. PPi is also provided through the PPi transporter ANKH (a homologue of the mouse progressive ankylosis gene product) from the cytoplasm, in which PPi is routinely formed by cellular metabolism. ANKH is distributed onthe plasma membrane of hypertrophic chondrocytes and osteoblasts. TNAP on the membrane of the matrix vesicles hydrolyzes PPi and yields Pi, thereby reducing the levels of the PPi inhibitor and promoting hydroxyapatite formation. |
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Formal Description Interaction-ID: 101996 |
gene/protein increases_transport of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | The concentration ratio of Pi to inorganic pyrophosphate (PPi) in the extracellular matrix is crucial in the second step of mineralization because PPi is an inhibitor of hydroxyapatite formation. Two mechanisms are used for PPi formation. PPi is formed in the extracellular matrix from ATP by the matrix vesicle membrane enzyme NPP1. PPi is also provided through the PPi transporter ANKH (a homologue of the mouse progressive ankylosis gene product) from the cytoplasm, in which PPi is routinely formed by cellular metabolism. ANKH is distributed onthe plasma membrane of hypertrophic chondrocytes and osteoblasts. TNAP on the membrane of the matrix vesicles hydrolyzes PPi and yields Pi, thereby reducing the levels of the PPi inhibitor and promoting hydroxyapatite formation. |
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Formal Description Interaction-ID: 101997 |
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| Drugbank entries | Show/Hide entries for |
| Comment | The concentration ratio of Pi to inorganic pyrophosphate (PPi) in the extracellular matrix is crucial in the second step of mineralization because PPi is an inhibitor of hydroxyapatite formation. Two mechanisms are used for PPi formation. PPi is formed in the extracellular matrix from ATP by the matrix vesicle membrane enzyme NPP1. PPi is also provided through the PPi transporter ANKH (a homologue of the mouse progressive ankylosis gene product) from the cytoplasm, in which PPi is routinely formed by cellular metabolism. ANKH is distributed onthe plasma membrane of hypertrophic chondrocytes and osteoblasts. TNAP on the membrane of the matrix vesicles hydrolyzes PPi and yields Pi, thereby reducing the levels of the PPi inhibitor and promoting hydroxyapatite formation. |
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Formal Description Interaction-ID: 101998 |
gene/protein increases_quantity of drug/chemical compound Calcium hydroxyapatite |
| Comment | In HPP patients, extracellular hydroxyapatite crystals are reduced and mineralization is impaired. HPP patients exhibit an increase in osteoid tissue that contains abundant nonmineralized bone extracellular matrix without hydroxyapatite crystals, leading to rickets and osteomalacia. |
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Formal Description Interaction-ID: 101999 |
disease Hypophosphatasia decreases_quantity of drug/chemical compound Calcium hydroxyapatite |
| Comment | A physiological role of TNAP is associated with neurotransmitter synthesis in the central nervous system. One of the physiological substrates of TNAP is pyridoxal 5'-phosphate, a derivative of vitamin B6, which is necessary for the biosynthesis of GABA, a cofactor of glutamic acid carboxylase in neuronal cells. GABA is known to act as a repressive neurotransmitter. For pyridoxal 5'-phosphate entry into cells, the phosphate moiety has to be first released, and then pyridoxal is incorporated into the cells, followed by rephosphorylation within the cells. It has been confirmed in fibroblasts from normal and HPP patients that TNAP hydrolyzes pyridoxal 5'-phosphate to release phosphate outside the cell membrane, and therefore a similar mechanism is presumed to operate in the neuronal cell membrane. Failure of this role of TNAP leads to epileptic seizures in HPP patients because reduced GABA in the neuronal cells results in hyperactivity of the central nervous system. |
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Formal Description Interaction-ID: 102025 |
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| Comment | A physiological role of TNAP is associated with neurotransmitter synthesis in the central nervous system. One of the physiological substrates of TNAP is pyridoxal 5'-phosphate, a derivative of vitamin B6, which is necessary for the biosynthesis of GABA, a cofactor of glutamic acid carboxylase in neuronal cells. GABA is known to act as a repressive neurotransmitter. For pyridoxal 5'-phosphate entry into cells, the phosphate moiety has to be first released, and then pyridoxal is incorporated into the cells, followed by rephosphorylation within the cells. It has been confirmed in fibroblasts from normal and HPP patients that TNAP hydrolyzes pyridoxal 5'-phosphate to release phosphate outside the cell membrane, and therefore a similar mechanism is presumed to operate in the neuronal cell membrane. Failure of this role of TNAP leads to epileptic seizures in HPP patients because reduced GABA in the neuronal cells results in hyperactivity of the central nervous system. |
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Formal Description Interaction-ID: 102026 |
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| Drugbank entries | Show/Hide entries for |
| Comment | A physiological role of TNAP is associated with neurotransmitter synthesis in the central nervous system. One of the physiological substrates of TNAP is pyridoxal 5'-phosphate, a derivative of vitamin B6, which is necessary for the biosynthesis of GABA, a cofactor of glutamic acid carboxylase in neuronal cells. GABA is known to act as a repressive neurotransmitter. For pyridoxal 5'-phosphate entry into cells, the phosphate moiety has to be first released, and then pyridoxal is incorporated into the cells, followed by rephosphorylation within the cells. It has been confirmed in fibroblasts from normal and HPP patients that TNAP hydrolyzes pyridoxal 5'-phosphate to release phosphate outside the cell membrane, and therefore a similar mechanism is presumed to operate in the neuronal cell membrane. Failure of this role of TNAP leads to epileptic seizures in HPP patients because reduced GABA in the neuronal cells results in hyperactivity of the central nervous system. |
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Formal Description Interaction-ID: 102027 |
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