Whyte M P, Mahuren J D, Vrabel L A, Coburn S P
J Clin Invest. 1985 Aug;76(2):752-6. doi: 10.1172/JCI112031.
Markedly increased circulating concentrations of pyridoxal-5'-phosphate (PLP) were found in each of 14 patients representing all clinical forms of hypophosphatasia, an inborn error characterized by deficient activity of the tissue nonspecific (bone/liver/kidney) isoenzyme of alkaline phosphatase (AP). The mean PLP concentration in plasma was 1174 nM (range, 214-3839 nM) in the patients and 57 +/- 26 nM (mean +/- SD) in 38 control subjects. In four affected children, urinary excretion of the PLP degradation product, 4-pyridoxic acid, was unremarkable during consumption of normal quantities of dietary vitamin B6. Our findings identify increased circulating PLP concentration as a marker for hypophosphatasia and provide further evidence that tissue nonspecific AP acts in vitamin B6 metabolism. Tissue nonspecific AP appears to function as an ectoenzyme to regulate extracellular but not intracellular levels of PLP substrate. Performing assays of circulating PLP concentration alone to assess vitamin B6 nutrition may be misleading in disorders associated with altered AP activity.
在14例代表各种临床类型低磷酸酯酶症的患者中，均发现循环中的磷酸吡哆醛-5'-磷酸（PLP）浓度显著升高。低磷酸酯酶症是一种先天性疾病，其特征是组织非特异性（骨/肝/肾）碱性磷酸酶（AP）同工酶活性缺乏。患者血浆中PLP的平均浓度为1174 nM（范围为214 - 3839 nM），而38名对照受试者的血浆PLP平均浓度为57±26 nM（平均值±标准差）。在4名患病儿童中，正常摄入膳食维生素B6期间，PLP降解产物4-吡哆酸的尿排泄量无异常。我们的研究结果确定循环中PLP浓度升高是低磷酸酯酶症的一个标志物，并进一步证明组织非特异性AP在维生素B6代谢中起作用。组织非特异性AP似乎作为一种胞外酶发挥作用，调节细胞外而非细胞内的PLP底物水平。仅通过检测循环中PLP浓度来评估维生素B6营养状况，在与AP活性改变相关的疾病中可能会产生误导。
