Alkaline phosphatase (ALP) is detected in most human tissues. However, ALP activity is routinely assayed using high concentrations of artificial colorimetric substrates in phosphate-free laboratory buffers at lethal pH. Hypophosphatasia (HPP) is the inborn-error-of-metabolism caused by loss-of-function mutation(s) of the gene that encodes the ALP isoenzyme expressed in bone, liver, kidney, and elsewhere and is therefore designated “tissue-nonspecific” ALP (TNSALP). Consequently, HPP harbors clues concerning the biological function of this phosphohydrolase that is anchored onto the surface of cells. The biochemical signature of HPP features low serum ALP activity (hypophosphat) together with elevated plasma levels of three natural substrates of TNSALP: i) phosphoethanolamine (PEA), a component of the linkage apparatus that binds ALPs and other proteins to the plasma membrane surface; ii) inorganic pyrophosphate (PPi), an inhibitor of bone and tooth mineralization; and iii) pyridoxal 5′-phosphate (PLP), the principal circulating vitameric form of vitamin B (B). Autosomal dominant and autosomal recessive inheritance involving several hundred mutations underlies the remarkably broad-ranging expressivity of HPP featuring tooth loss often with muscle weakness and rickets or osteomalacia. Thus, HPP associates the “bone” isoform of TNSALP with biomineralization, whereas the physiological role of the “liver”, “kidney”, and other isoforms of TNSALP remains uncertain.

中文翻译：

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吡哆醇激发反映了儿科低磷酸酯酶症的严重程度，从而检查了组织非特异性碱性磷酸酶在维生素 B6 代谢中的作用

大多数人体组织中都检测到碱性磷酸酶 (ALP)。然而，ALP 活性通常是在致死 pH 值的无磷酸盐实验室缓冲液中使用高浓度的人工比色底物进行测定。低磷酸酯酶症 (HPP) 是一种先天性代谢错误，由编码在骨、肝脏、肾脏和其他部位表达的 ALP 同工酶的基因功能丧失突变引起，因此被称为“组织非特异性” ” ALP（TNSALP）。因此，HPP 提供了有关这种固定在细胞表面的磷酸水解酶的生物学功能的线索。 HPP 的生化特征包括血清 ALP 活性（低磷酸盐）低以及 TNSALP 三种天然底物血浆水平升高： i) 磷酸乙醇胺 (PEA)，一种将 ALP 和其他蛋白质结合到质膜表面的连接装置的组成部分； ii) 无机焦磷酸盐 (PPi)，骨和牙齿矿化的抑制剂； iii) 5'-磷酸吡哆醛 (PLP)，维生素 B (B) 的主要循环维生素体形式。涉及数百个突变的常染色体显性和常染色体隐性遗传构成了 HPP 非常广泛的表达性的基础，其特征是牙齿脱落，通常伴有肌肉无力和佝偻病或骨软化症。因此，HPP 将 TNSALP 的“骨”亚型与生物矿化联系起来，而 TNSALP 的“肝”、“肾”和其他亚型的生理作用仍不确定。