Pieters R, Veerman A J
Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
Med Hypotheses. 1988 Sep;27(1):77-80. doi: 10.1016/0306-9877(88)90088-6.
Purine nucleotides become available for a cell by two routes, namely purine de novo synthesis and the purine salvage pathway. 5'Nucleotidase is a purine pathway enzyme and is present in two forms. Cytoplasmic 5'nucleotidase (cyto 5'NT) catalyzes the intracellular degradation of purine nucleotides into their corresponding nucleosides. The plasma membrane bound form (ecto 5'NT) has its active site facing the external medium. Its function is the extracellular dephosphorylation of nucleotides, to which cells are generally impermeable, into nucleosides and the transport of these nucleosides through the cell membrane. Lymphoblastic 5'NT activity varies between different children with common-ALL. 5'NT positive cases have a higher relapse rate and thus a poorer prognosis than 5'NT negative cases. This can be explained by two hypotheses which are not mutually exclusive: 1. Rescue hypothesis. When purine de novo synthesis is blocked by methotrexate (MTX) and/or 6-mercaptopurine (6-MP), the malignant cell has to rely on the purine salvage pathway. This pathway depends on the ecto-5'NT activity. So, leukemic cells might be resistant to MTX and/or 6-MP because of ecto-5'NT activity. 2. Breakdown hypothesis. Leukemic cells are resistant to 6-MP because of the breakdown of the toxic nucleotide form of 6-MP into the nucleoside form by cyto-5'NT.
嘌呤核苷酸通过两条途径进入细胞，即嘌呤从头合成途径和嘌呤补救途径。5'-核苷酸酶是嘌呤途径中的一种酶，有两种形式。细胞质5'-核苷酸酶（cyto 5'NT）催化嘌呤核苷酸在细胞内降解为相应的核苷。质膜结合形式（ecto 5'NT）的活性位点面向外部介质。其功能是将细胞通常不可通透的核苷酸在细胞外脱磷酸化为核苷，并将这些核苷转运穿过细胞膜。淋巴细胞性5'-核苷酸酶活性在不同的普通型急性淋巴细胞白血病儿童中有所不同。5'-核苷酸酶阳性病例的复发率较高，因此预后比5'-核苷酸酶阴性病例差。这可以用两种并非相互排斥的假说来解释：1. 挽救假说。当嘌呤从头合成被甲氨蝶呤（MTX）和/或6-巯基嘌呤（6-MP）阻断时，恶性细胞必须依赖嘌呤补救途径。该途径依赖于ecto-5'NT活性。因此，白血病细胞可能由于ecto-5'NT活性而对MTX和/或6-MP耐药。2. 分解假说。白血病细胞对6-MP耐药是因为cyto-5'NT将6-MP的有毒核苷酸形式分解为核苷形式。
