There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue-nonspecific). The first three are located together on chromosome 2, whereas the tissue-nonspecific form is located on chromosome 1. The product of this gene is a membrane-bound glycosylated enzyme that is not expressed in any particular tissue and is, therefore, referred to as the tissue-nonspecific form of the enzyme. The exact physiological function of the alkaline phosphatases is not known. A proposed function of this form of the enzyme is matrix mineralization. However, mice that lack a functional form of this enzyme show normal skeletal development.
This enzyme has been linked directly to a disorder known as hypophosphatasia, a disorder that is characterized by hypercalcemia and includes skeletal defects. The character of this disorder can vary, however, depending on the specific mutation, since this determines age of onset and severity of symptoms.
The severity of symptoms ranges from premature loss of deciduous teeth with no bone abnormalities to stillbirth depending upon which amino acid
is changed in the ALPL gene. Mutations in the ALPL gene lead to varying low activity of the enzyme tissue-nonspecific alkaline phosphatase (TNSALP) resulting in hypophosphatasia (HPP). There are different clinical forms of HPP which can be inherited by an autosomal recessive trait or autosomal dominant trait, the former causing more severe forms of the disease. Alkaline phosphatase allows for mineralization of calcium and phosphorus by bones and teeth. ALPL gene mutation leads to insufficient TNSALP enzyme and allows for an accumulation of chemicals such as inorganic pyrophosphate to indirectly cause elevated calcium levels in the body and lack of bone calcification.
The mutation E174K, where a glycine is converted to an alanine amino acid at the 571st position of its respective polypeptide chain, is a result of an ancestral mutation that occurred in Caucasians and shows a mild form of HPP.
^Swallow DM, Povey S, Parkar M, Andrews PW, Harris H, Pym B, Goodfellow P (July 1986). "Mapping of the gene coding for the human liver/bone/kidney isozyme of alkaline phosphatase to chromosome 1". Annals of Human Genetics. 50 (Pt 3): 229–35. doi:10.1111/j.1469-1809.1986.tb01043.x. PMID3446011.
^ abcHérasse M, Spentchian M, Taillandier A, Mornet E (October 2002). "Evidence of a founder effect for the tissue-nonspecific alkaline phosphatase (TNSALP) gene E174K mutation in hypophosphatasia patients". European Journal of Human Genetics. 10 (10): 666–8. doi:10.1038/sj.ejhg.5200857. PMID12357339.
^Nasu M, Ito M, Ishida Y, Numa N, Komaru K, Nomura S, Oda K (December 2006). "Aberrant interchain disulfide bridge of tissue-nonspecific alkaline phosphatase with an Arg433→Cys substitution associated with severe hypophosphatasia". The FEBS Journal. 273 (24): 5612–24. doi:10.1093/oxfordjournals.jbchem.a022032. PMID17212778.
^Ishida Y, Komaru K, Ito M, Amaya Y, Kohno S, Oda K (July 2003). "Tissue-nonspecific alkaline phosphatase with an Asp(289)→Val mutation fails to reach the cell surface and undergoes proteasome-mediated degradation". Journal of Biochemistry. 134 (1): 63–70. doi:10.1093/jb/mvg114. PMID12944372.
Nishihara Y, Hayashi Y, Adachi T, Koyama I, Stigbrand T, Hirano K (December 1992). "Chemical nature of intestinal-type alkaline phosphatase in human kidney". Clinical Chemistry. 38 (12): 2539–42. PMID1458595.
Weiss MJ, Ray K, Henthorn PS, Lamb B, Kadesch T, Harris H (August 1988). "Structure of the human liver/bone/kidney alkaline phosphatase gene". The Journal of Biological Chemistry. 263 (24): 12002–10. PMID3165380.
Smith M, Weiss MJ, Griffin CA, Murray JC, Buetow KH, Emanuel BS, Henthorn PS, Harris H (February 1988). "Regional assignment of the gene for human liver/bone/kidney alkaline phosphatase to chromosome 1p36.1-p34". Genomics. 2 (2): 139–43. doi:10.1016/0888-7543(88)90095-X. PMID3410475.
Garattini E, Hua JC, Pan YC, Udenfriend S (March 1986). "Human liver alkaline phosphatase, purification and partial sequencing: homology with the placental isozyme". Archives of Biochemistry and Biophysics. 245 (2): 331–7. doi:10.1016/0003-9861(86)90223-7. PMID3954357.
Sato N, Takahashi Y, Asano S (February 1994). "Preferential usage of the bone-type leader sequence for the transcripts of liver/bone/kidney-type alkaline phosphatase gene in neutrophilic granulocytes". Blood. 83 (4): 1093–101. PMID7509208.
Orimo H, Hayashi Z, Watanabe A, Hirayama T, Hirayama T, Shimada T (September 1994). "Novel missense and frameshift mutations in the tissue-nonspecific alkaline phosphatase gene in a Japanese patient with hypophosphatasia". Human Molecular Genetics. 3 (9): 1683–4. doi:10.1093/hmg/3.9.1683. PMID7833929.
Greenberg CR, Taylor CL, Haworth JC, Seargeant LE, Philipps S, Triggs-Raine B, Chodirker BN (July 1993). "A homoallelic Gly317-->Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites". Genomics. 17 (1): 215–7. doi:10.1006/geno.1993.1305. PMID8406453.
Ozono K, Yamagata M, Michigami T, Nakajima S, Sakai N, Cai G, Satomura K, Yasui N, Okada S, Nakayama M (December 1996). "Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia". The Journal of Clinical Endocrinology and Metabolism. 81 (12): 4458–61. doi:10.1210/jc.81.12.4458. PMID8954059.
Orimo H, Goseki-Sone M, Sato S, Shimada T (June 1997). "Detection of deletion 1154-1156 hypophosphatasia mutation using TNSALP exon amplification". Genomics. 42 (2): 364–6. doi:10.1006/geno.1997.4733. PMID9192863.
Sugimoto N, Iwamoto S, Hoshino Y, Kajii E (1998). "A novel missense mutation of the tissue-nonspecific alkaline phosphatase gene detected in a patient with hypophosphatasia". Journal of Human Genetics. 43 (3): 160–4. doi:10.1007/s100380050061. PMID9747027.
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