Potential enzymatic functions and structural visualization of TNAP. (A) Depiction of potential TNAP substrates. (B) Schematic depiction of a predicted homology model of TNAP’s dimerized 3D structure (https://swissmodel.expasy.org/; SWISS-MODEL: P05186 (PPBT_HUMAN); homology model according to the template: 3mk1.1.B “Refinement of placental alkaline phosphatase complexed with nitrophenyl”) and magnified view of the active site [26,27,28]. Figure 1B was modified according to SWISS-MODEL database terms of use and is licensed under a Creative Commons Attribution 4.0 (https://creativecommons.org/licenses/by-sa/4.0/). ATP/ADP/AMP: adenosine tri-/di-/monophosphate, GPI-anchor: glycosyl-phosphatidylinositol anchor, Pi: phosphate, PLP: pyridoxal-5′-phosphate, p-OPN: phosphorylated osteopontin, PPi: inorganic pyrophosphate, TNAP: tissue-nonspecific alkaline phosphatase.

Schematic model of TNAP function within mineralizing cells (Modified according to Yadav et al. 2014 [67]). ATP: adenosine triphosphate, ANKH: progressive ankylosis protein homolog, ENPP1: ectonucleotide pyrophosphatase/ phosphodiesterase family member 1, SPP1/OPN: secreted phosphoprotein 1/osteopontin, Phospho1: phosphoethanolamine/phosphocholine phosphatase, Pi: Phosphate, PiT-1/2: sodium-dependent phosphate transporters 1 and 2, p-OPN: phosphorylated osteopontin, PPi: inorganic pyrophosphate, TNAP: tissue-nonspecific alkaline phosphatase.

The role of TNAP within the purinergic signaling. ATP/ADP/AMP: adenosine tri-/die-/monophosphate, cAMP: cyclic adenosine monophosphate, DAG: diacylglycerol, CD39/ENTPDase1: ectonucleoside triphosphate diphosphohydrolase 1, IP3: Inositol trisphosphate, CD73/NT5E: ecto-5′-nucleotidase, PIP2: phosphatidylinositol 4,5-bisphosphate, PKA: phosphokinase A, PLC: phospholipase C, TNAP: tissue-nonspecific alkaline phosphatase.

TNAP function is linked to PLP/cofactor, neurotrophic factor and myelin synthesis. (A) TNAP’s influence on the GABA synthesis. (B) TNAP’s role in the catecholamine and serotonin synthesis. (C) TNAP’s impact on purinergic signaling. (D) TNAP’s role in the myelin synthesis pathway. HTP: 5-hydroxytryptophan, AADC: aromatic L-amino acid decarboxylase, ATP/ADP/AMP: adenosine tri-/di-/monophosphate, BBB: blood–brain barrier, GABA: gamma-aminobutyric acid, GAD: glutamate decarboxylase, L-DOPA: levodopa, PDXK: pyridoxal kinase, PLP: pyridoxal-5′-phosphate, TNAP: tissue-nonspecific alkaline phosphatase.

Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Biomolecules