AP-TNAP (human, recombinant)

Alkaline phosphatase, tissue non-specific enzyme (AP-TNAP) is a monoester phosphohydrolase with roles in bone mineralization and early embryonic development of the CNS.^1,2,3 It is ubiquitously expressed but is enriched in liver, bone, kidney, and the CNS and is found in the cytoplasmic membrane. AP-TNAP hydrolyzes extracellular inorganic pyrophosphate, a mineralization inhibitor, to facilitate the deposition of hydroxyapatite in bones and teeth.³ It also converts pyridoxal-5’-phosphate, an active form of vitamin B₆, into pyridoxal, which functions as a cofactor for the synthesis of enzymes involved in the metabolism of several neurotransmitters. Mutations in ALPL, the gene encoding AP-TNAP, are associated with hypophosphatasia, an inborn error of metabolism characterized by severe skeletal hypomineralization, respiratory problems, and seizures, among other symptoms.^4,5 AP-TNAP activity is increased in the hippocampus of patients with Alzheimer’s disease compared with age-related controls.³ Cayman’s AP-TNAP (human, recombinant) protein can be used for enzyme activity assay and Western blot (WB) applications. This protein consists of 496 amino acids, has a calculated molecular weight of 55 kDa, and a predicted N-terminus of Leu18 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, this protein has an apparent molecular mass of 65 kDa due to glycosylation.

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1. Whyte, M.P. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann. N. Y. Acad. Sci. 1192, 190-200 (2010).

2. Sato, M., Saitoh, I., Kiyokawa, Y., et al. Tissue-nonspecific alkaline phosphatase, a possible mediator of cell maturation: Towards a new paradigm. Cells 10(12), 3338 (2021).

3. Sebastián-Serrano, Á., de Diego-García, L., Martínez-Frailes, C., et al. Tissue-nonspecific alkaline phosphatase regulates purinergic transmission in the central nervous system during development and disease. Comput. Struct. Biotechnol. J. 13, 95-100 (2014).

4. Del Angel, G., Reynders, J., Negron, C., et al. Large-scale in vitro functional testing and novel variant scoring via protein modeling provide insights into alkaline phosphatase activity in hypophosphatasia. Hum. Mutat. 41(7), 1250-1262 (2020).

5. Whyte, M.P. Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. Nat. Rev. Endocrinol. 12(4), 233-246 (2016).