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Tissue-nonspecific alkaline phosphatase

Hessle L, Johnson KA, Anderson HC, Narisawa S, Sali A, Coding JW, Terkeltaub R, Millan JL. 2002. Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci USA 99 9445—9. [Pg.556]

Nouwen EJ, De Broe ME. Fluman intestinal versus tissue-nonspecific alkaline phosphatase as complementary urinary markers for the proximal tubule. Kidney Int 1994 46(Suppl 47) S43-51. [Pg.124]

A physiologic phosphate concentration is required for bone mineralization. Lowering the concentration prevents mineralization, but raising it does not ensure precipitation because pyrophosphate is present to inhibit precipitation. The concentration of PPi in cartilage and bone is controlled by three enzymes, two on the outer surface of matrix vesicles (Fig. 9.5b). One is tissue-nonspecific alkaline phosphatase (TNAP), which decreases stromal pyrophosphate and the other is NTP-PPi hydrolase (also called plasma cell membrane glycoprotein-1), which increases it. The progressive ankylosis gene product (ANK protein) is expressed by osteoblasts to add to the pyrophosphate of the osteoid matrix from osteoblast cytosol. [Pg.140]

Mineralization therefore occurs in bone because of the exclusive co-expression in osteoblasts of type I collagen and tissue-nonspecific alkaline phosphatase (TNAP). The abnormal appearance of TNAP in any cell that also produces fibrillar collagen (ectopic TNAP expression) gives rise to pathological (nonbacterial) mineralization, which is outside the scope of this text. [Pg.140]

Osteoblasts secrete osteoid, a matrix rich in type I collagen fibers and vesicles. Precipitation of calcium phosphate is inhibited by a high concentration of pyrophosphate in stromal interstitial fluids, and a high concentration also of albumin and citrate in blood plasma. Pyrophosphate is derived from (1) transport out of the cytosol, and (2) synthesis from nucleoside triphosphates in the stromal interstitial fluid that permeates the osteoid matrix. Precipitation occurs only when calcium and phosphate ions are taken up into vesicles whose inner membrane is composed of phosphatidylserine. The high concentration of calcium and phosphate ions in the vesicle is mediated by annexin and type HI Pi Na-dependent transporters. This overwhelms the pyrophosphate and nucleation occurs. As the precipitate grows and ruptures the membrane, tissue-nonspecific alkaline phosphatase is activated to remove pyrophosphate from the osteoid matrix fluid so that calcium phosphate precipitates around phosphorylated serine residues within the collagen fibers. [Pg.141]

Fig.9.8 Removal of pyrophosphate is necessary for precipitation. Pyrophosphate (PPi) inhibits the precipitation of calcium phosphate. In the bone matrix, PC-1 (red) is the major producer of PPi from nucleotide triphosphates (NTPs, thick arrow on left) and ANK is a minor producer by transporting it from the cytosol of osteoblasts. TNAP (green) causes mineralization by its phosphatase activity converting PPi to two molecules of Pi. TNAP also generates Pi directly from NTPs and PPi, but most Pi and most Ca2+ are derived directly from the diet (thick arrow on right) (Slightly modified from Fig. 4 in Hessle L et al. (2002) Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proceedings of the National Academy of Sciences 99 9445-9449. Copyright (2002) National Academy of Sciences, U.S.A)... Fig.9.8 Removal of pyrophosphate is necessary for precipitation. Pyrophosphate (PPi) inhibits the precipitation of calcium phosphate. In the bone matrix, PC-1 (red) is the major producer of PPi from nucleotide triphosphates (NTPs, thick arrow on left) and ANK is a minor producer by transporting it from the cytosol of osteoblasts. TNAP (green) causes mineralization by its phosphatase activity converting PPi to two molecules of Pi. TNAP also generates Pi directly from NTPs and PPi, but most Pi and most Ca2+ are derived directly from the diet (thick arrow on right) (Slightly modified from Fig. 4 in Hessle L et al. (2002) Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proceedings of the National Academy of Sciences 99 9445-9449. Copyright (2002) National Academy of Sciences, U.S.A)...
ALPL NM 000478 TNAP Tissue-nonspecific alkaline phosphatase, TNSALP liver-bone-kidney-type AP Developing nervous system, skeletal tissues, liver, kidney Bone and dental mineralization... [Pg.29]

Residues determining the binding specificity of uncompetitive inhibitors to tissue-nonspecific alkaline phosphatase. J Bone Miner Res 19 1862-1872... [Pg.46]

Knockdown of tissue nonspecific alkaline phosphatase impairs neural stem cell proliferation and differentiation. Neurosci Lett 4851208-211... [Pg.48]

Dahl R, Sergienko EA, Su Y et al (2009) Discovery and validation of a series of aryl sulfonamides as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). J Med Chem 52 6919-6925... [Pg.50]

Diaz-Hemandez M, Gomez-Ramos A, Rubio A et al (2010) Tissue-nonspecific alkaline phosphatase promotes the neurotoxicity effect of extracellular tau. J Biol Chem 285 32539-32548... [Pg.50]

Robotic Implementation of Assays Tissue-Nonspecific Alkaline Phosphatase (TNAP) Case Study... [Pg.53]

Key words High-throughput screens, HTS, Chemical libraries. Laboratory automation. Automated assays. Robotics, Phosphatase assays. Assay development. Implementation, Enzymes, Alkaline phosphatases. Tissue-nonspecific alkaline phosphatase (TNAP)... [Pg.53]

Sergienko EA, Millan JL (2010) High-throughput screening of tissue-nonspecific alkaline phosphatase for identification of effectors with diverse modes of action. Nat Protoc 5 1431-1439... [Pg.84]

Sergienko E, Su Y, Chan X et al (2009) Identification and characterization of novel tissue-nonspecific alkaline phosphatase inhibitors with diverse modes of action. J Biomol Screen 14 824-837... [Pg.84]

Key words AlkaKne phosphatase, Tissue-nonspecific alkaline phosphatase. Blood plasma. Biomarker,... [Pg.103]

Chung TD, Sergienko E, Millan JL (2010) Assay format as a critical success factor for identification of novel inhibitor chemotypes of tissue-nonspecific alkaline phosphatase from high-throughput screening. Molecules 15 3010-3037... [Pg.112]

It has been hypothesized that phosphate accelerates this chondro-osteogenic conversion by inducing expression of runt-related transcription factor 2 (RUNX2), osteocalcin and tissue-nonspecific alkaline phosphatase (TNAP) [2]. Elevated TNAP further favors vascular calcification by hydrolyzing the calcification inhibitor inorganic pyrophosphate (PPi) [3-6]. In the Enppl mouse model of GACI, inhibition of TNAP can restore PPj to sufficient levels to maintain normal mineralization [3]. [Pg.125]

Key words Alkaline phosphatase. Intestinal alkaline phosphatase. Tissue-nonspecific alkaline phosphatase, Placental alkaline phosphatase. High throughput assay, Chemilmninescence, CDP-star, Inhibition, Activation, Structure-activity relationship... [Pg.135]

Alkaline phosphatase (AP orthophosphoric monoester phospho-hydrolase, EC 3.1.3.1) isozymes are present in a wide range of species from bacteria to man and are capable of dephosphorylation and transphosphorylation of a broad spectrum of substrates in vitro [1]. Their broad snbstrate specificity and localization on the outside leaf of the cytoplasmic membrane suggests potential involvement in numerons extracellular processes. In humans, four isozymes of APs have been identified. One of them, tissue-nonspecific alkaline phosphatase (TNAP), is ubiquitously expressed, demonstrating especially high level of expression in bone, liver and kidney tissues. Three other isozymes demonstrate tissue-specific... [Pg.135]

See other pages where Tissue-nonspecific alkaline phosphatase is mentioned: [Pg.637]    [Pg.71]    [Pg.6]    [Pg.8]    [Pg.27]    [Pg.28]    [Pg.48]    [Pg.53]    [Pg.55]    [Pg.85]    [Pg.85]    [Pg.103]    [Pg.103]    [Pg.116]    [Pg.135]   


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