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Citations to this article

Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy.
M P Whyte, … , J D Mahuren, S P Coburn
M P Whyte, … , J D Mahuren, S P Coburn
Published April 1, 1995
Citation Information: J Clin Invest. 1995;95(4):1440-1445. https://doi.org/10.1172/JCI117814.
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Research Article Article has an altmetric score of 9

Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy.

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Abstract

Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.

Authors

M P Whyte, M Landt, L M Ryan, R A Mulivor, P S Henthorn, K N Fedde, J D Mahuren, S P Coburn

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Citations to this article in year 2012 (7)

Title and authors Publication Year
Characterization of Spontaneous Bone Marrow Recovery after Sublethal Total Body Irradiation: Importance of the Osteoblastic/Adipocytic Balance
G Poncin, A Beaulieu, C Humblet, A Thiry, K Oda, J Boniver, MP Defresne
PloS one 2012
Cellular function and molecular structure of ecto-nucleotidases
H Zimmermann, M Zebisch, N Sträter
Purinergic Signalling 2012
Hypophosphatasia
MP Whyte
Pediatric Bone 2012
Ablation of TNAP function compromises myelination and synaptogenesis in the mouse brain
J Hanics, J Barna, J Xiao, JL Millán, C Fonta, L Négyessy
Cell and Tissue Research 2012
Pediatric Bone
M Bastepe, H Jüppner, RV Thakker
Pediatric Bone 2012
Hypophosphatasia - pathophysiology and treatment
José Luis Millán, Horacio Plotkin
Actualizaciones en osteologia 2012
Characterization of Spontaneous Bone Marrow Recovery after Sublethal Total Body Irradiation: Importance of the Osteoblastic/Adipocytic Balance
G Poncin, A Beaulieu, C Humblet, A Thiry, K Oda, J Boniver, MP Defresne, EJ Bernhard
PloS one 2012

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