Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease
Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorga...
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MDPI AG
2020-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/12/1648 |
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| author | Daniel Liedtke Christine Hofmann Franz Jakob Eva Klopocki Stephanie Graser |
| author_facet | Daniel Liedtke Christine Hofmann Franz Jakob Eva Klopocki Stephanie Graser |
| author_sort | Daniel Liedtke |
| collection | DOAJ |
| description | Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the <i>ALPL</i> gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme’s role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish. |
| first_indexed | 2024-03-10T14:14:48Z |
| format | Article |
| id | doaj.art-9ee5f5f5444e4188ac353581a1ac7f92 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T14:14:48Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-9ee5f5f5444e4188ac353581a1ac7f922023-11-20T23:55:39ZengMDPI AGBiomolecules2218-273X2020-12-011012164810.3390/biom10121648Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in DiseaseDaniel Liedtke0Christine Hofmann1Franz Jakob2Eva Klopocki3Stephanie Graser4Institute for Human Genetics, Biocenter, Julius-Maximilians-University Würzburg, 97074 Würzburg, GermanySection of Pediatric Rheumatology and Osteology, University Children’s Hospital of Würzburg, 97080 Würzburg, GermanyBernhard-Heine-Center for Locomotion Research, Julius-Maximilians-University Würzburg, 97076 Würzburg, GermanyInstitute for Human Genetics, Biocenter, Julius-Maximilians-University Würzburg, 97074 Würzburg, GermanyBernhard-Heine-Center for Locomotion Research, Julius-Maximilians-University Würzburg, 97076 Würzburg, GermanyTissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the <i>ALPL</i> gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme’s role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.https://www.mdpi.com/2218-273X/10/12/1648TNAPhypophosphatasiaHPPzebrafishmineralization<i>ALPL</i> |
| spellingShingle | Daniel Liedtke Christine Hofmann Franz Jakob Eva Klopocki Stephanie Graser Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease Biomolecules TNAP hypophosphatasia HPP zebrafish mineralization <i>ALPL</i> |
| title | Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease |
| title_full | Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease |
| title_fullStr | Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease |
| title_full_unstemmed | Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease |
| title_short | Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease |
| title_sort | tissue nonspecific alkaline phosphatase a gatekeeper of physiological conditions in health and a modulator of biological environments in disease |
| topic | TNAP hypophosphatasia HPP zebrafish mineralization <i>ALPL</i> |
| url | https://www.mdpi.com/2218-273X/10/12/1648 |
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