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One such ectoenzyme \u2014 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\u2009=\u2009340\u2005\u00b5M\u2009\u00b1\u200944; SmNACE, KM\u2009=\u200949\u2005\u00b5M\u2009\u00b1\u20094. 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.<\/jats:p>","DOI":"10.1042\/bcj20210784","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T09:24:56Z","timestamp":1653038696000},"page":"1165-1180","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["NAD-catabolizing ectoenzymes of <i>Schistosoma mansoni<\/i>"],"prefix":"10.1042","volume":"479","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4197-3867","authenticated-orcid":false,"given":"Catherine S.","family":"Nation","sequence":"first","affiliation":[{"name":"Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akram A.","family":"Da'Dara","sequence":"additional","affiliation":[{"name":"Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Skelly","sequence":"additional","affiliation":[{"name":"Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"2022060812530169400_BCJ-2021-0784C1","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1016\/s0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","year":"2014","journal-title":"Lancet"},{"key":"2022060812530169400_BCJ-2021-0784C2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.curtheres.2019.06.001","article-title":"Schistosomiasis: life cycle, diagnosis, and control","volume":"91","year":"2019","journal-title":"Curr. 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