Infection with schistosomes (blood flukes) can result in the debilitating disease schistosomiasis. These parasites survive in their host for many years, and we hypothesize that proteins on their tegumental surface, interacting with the host microenvironment, facilitate longevity. One such ectoenzyme — the nucleotide pyrophosphatase/phosphodiesterase SmNPP5 can cleave ADP (to prevent platelet aggregation) and NAD (likely preventing Treg apoptosis). A second tegumental ectoenzyme, the glycohydrolase SmNACE, also catabolizes NAD. Here, we undertake a comparative biochemical characterization of these parasite ectoenzymes. Both are GPI-linked and exhibit different optimal pH ranges. While SmNPP5 requires divalent cations, SmNACE does not. The KM values of the two enzymes for NAD at physiological pH differ: SmNPP5, KM = 340 µM ± 44; SmNACE, KM = 49 µM ± 4. NAD cleavage by each enzyme yields different products. SmNPP5 cleaves NAD to form nicotinamide mononucleotide (NMN) and AMP, whereas SmNACE cleaves NAD to generate nicotinamide (NAM) and adenosine diphosphate ribose (ADPR). Each enzyme can process the other's reaction product. Thus, SmNACE cleaves NMN (to yield NAM and ribose phosphate) and SmNPP5 cleaves ADPR (yielding AMP and ribose phosphate). Metabolomic analysis of plasma containing adult worms supports the idea that these cleavage pathways are active in vivo. We hypothesize that a primary function of SmNPP5 is to cleave NAD to control host immune cell function and a primary function of SmNACE is to cleave NMN to generate the vital nutrient nicotinamide (vitamin B3) for convenient uptake by the worms. Chemical inhibition of one or both ectoenzymes could upset worm metabolism and control schistosome infection.

中文翻译：

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曼氏血吸虫 NAD 分解代谢胞外酶

感染血吸虫（血吸虫）可导致使人衰弱的血吸虫病。这些寄生虫在它们的宿主中存活了很多年，我们假设它们外皮表面的蛋白质与宿主微环境相互作用，有助于长寿。一种这样的胞外酶——核苷酸焦磷酸酶/磷酸二酯酶 SmNPP5 可以切割 ADP（以防止血小板聚集）和 NAD（可能防止 Treg 凋亡）。第二种外膜外酶，即糖水解酶 SmNACE，也分解代谢 NAD。在这里，我们对这些寄生虫外酶进行了比较生化表征。两者都是 GPI 连接的，并表现出不同的最佳 pH 范围。虽然 SmNPP5 需要二价阳离子，但 SmNACE 不需要。两种酶在生理 pH 下对 NAD 的 KM 值不同：SmNPP5，KM = 340 µM ± 44；斯姆纳斯，KM = 49 µM ± 4。每种酶对 NAD 的切割产生不同的产物。SmNPP5 裂解 NAD 形成烟酰胺单核苷酸 (NMN) 和 AMP，而 SmNACE 裂解 NAD 生成烟酰胺 (NAM) 和二磷酸腺苷核糖 (ADPR)。每种酶都可以加工其他的反应产物。因此，SmNACE 切割 NMN（产生 NAM 和磷酸核糖），而 SmNPP5 切割 ADPR（产生 AMP 和磷酸核糖）。对含有成虫的血浆进行的代谢组学分析支持了这些裂解途径在体内是活跃的这一观点。我们假设 SmNPP5 的主要功能是切割 NAD 以控制宿主免疫细胞功能，而 SmNACE 的主要功能是切割 NMN 以产生重要的营养烟酰胺（维生素 B3）以方便蠕虫摄取。