PUBLICATION

Tissue-Nonspecific Alkaline Phosphatase-A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease

Authors
Liedtke, D., Hofmann, C., Jakob, F., Klopocki, E., Graser, S.
ID
ZDB-PUB-201212-29
Date
2020
Source
Biomolecules   10(12): (Review)
Registered Authors
Klopocki, Eva, Liedtke, Daniel
Keywords
ALPL, HPP, TNAP, craniosynostosis, hypophosphatasia, mineralization, nervous system, teeth, zebrafish
MeSH Terms
  • Alkaline Phosphatase/deficiency
  • Alkaline Phosphatase/genetics*
  • Animals
  • Anxiety/enzymology
  • Anxiety/genetics*
  • Anxiety/pathology
  • Bone and Bones/enzymology*
  • Bone and Bones/pathology
  • Calcification, Physiologic/genetics
  • Depression/enzymology
  • Depression/genetics*
  • Depression/pathology
  • Diphosphates/metabolism
  • Disease Models, Animal
  • Gene Expression
  • Humans
  • Hypophosphatasia/enzymology
  • Hypophosphatasia/genetics*
  • Hypophosphatasia/pathology
  • Mutation
  • Seizures/enzymology
  • Seizures/genetics*
  • Seizures/pathology
  • Severity of Illness Index
  • Tooth/enzymology*
  • Tooth/growth & development
  • Vitamin B 6/metabolism
PubMed
33302551 Full text @ Biomolecules
Abstract
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 ALPL 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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping