{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:18:39Z","timestamp":1790162319263,"version":"4.1.0"},"reference-count":40,"publisher":"Cambridge University Press (CUP)","issue":"5","license":[{"start":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T00:00:00Z","timestamp":1541376000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The kinetoplastid parasite<jats:italic>Trypanosoma brucei<\/jats:italic>causes African trypanosomiasis in both humans and animals. Infections place a significant health and economic burden on developing nations in sub-Saharan Africa, but few effective anti-parasitic treatments are currently available. Hence, there is an urgent need to identify new leads for drug development. The<jats:italic>T. brucei<\/jats:italic>neutral sphingomyelinase (TbnSMase) was previously established as essential to parasite survival, consequently being identified as a potential drug target. This enzyme may catalyse the single route to sphingolipid catabolism outside the<jats:italic>T. brucei<\/jats:italic>lysosome. To obtain new insight into parasite sphingolipid catabolism, the substrate specificity of TbnSMase was investigated using electrospray ionization tandem mass spectrometry (ESI-MS\/MS). Recombinant TbnSMase was shown to degrade sphingomyelin, inositol-phosphoceramide and ethanolamine-phosphoceramide sphingolipid substrates, consistent with the sphingolipid complement of the parasites. TbnSMase also catabolized ceramide-1-phosphate, but was inactive towards sphingosine-1-phosphate. The broad-range specificity of this enzyme towards sphingolipid species is a unique feature of TbnSMase. Additionally, ESI-MS\/MS analysis revealed previously uncharacterized activity towards<jats:italic>lyso<\/jats:italic>-phosphatidylcholine despite the enzyme's inability to degrade phosphatidylcholine. Collectively, these data underline the enzyme's importance in choline homoeostasis and the turnover of sphingolipids in<jats:italic>T. brucei<\/jats:italic>.<\/jats:p>","DOI":"10.1017\/s0031182018001853","type":"journal-article","created":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T08:50:44Z","timestamp":1541407844000},"page":"604-616","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":4,"title":["Substrate specificity of the neutral sphingomyelinase from<i>Trypanosoma brucei<\/i>"],"prefix":"10.1017","volume":"146","author":[{"given":"Emily A.","family":"Dickie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1994-2009","authenticated-orcid":false,"given":"Terry K.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2018,11,5]]},"reference":[{"key":"S0031182018001853_ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2009.06.002"},{"key":"S0031182018001853_ref40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031059"},{"key":"S0031182018001853_ref38","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601565"},{"key":"S0031182018001853_ref36","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00037-11"},{"key":"S0031182018001853_ref37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07151.x"},{"key":"S0031182018001853_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(99)00002-X"},{"key":"S0031182018001853_ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2006.04.028"},{"key":"S0031182018001853_ref18","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-090110-102913"},{"key":"S0031182018001853_ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2010.04.001"},{"key":"S0031182018001853_ref30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06393.x"},{"key":"S0031182018001853_ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2013.10.024"},{"key":"S0031182018001853_ref6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.2011.00533.x"},{"key":"S0031182018001853_ref34","unstructured":"World Health Organization (2017 a) Trypansomiasis, human African (sleeping sickness). 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