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Substrate specificity of the neutral sphingomyelinase from Trypanosoma brucei

Research output: Contribution to journalArticlepeer-review

Author(s)

Emily A. Dickie, Simon A. Young, Terry K. Smith

School/Research organisations

Abstract

The kinetoplastid parasite Trypanosoma brucei 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 T. brucei 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 T. brucei 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 lyso-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 T. brucei.
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Details

Original languageEnglish
Pages (from-to)604-616
Number of pages13
JournalParasitology
Volume146
Issue number5
Early online date5 Nov 2018
DOIs
Publication statusPublished - Apr 2019

    Research areas

  • Activity assay, Choline, Enzyme, Lipid catabolism, Lipid extraction, Mass spectrometry, Sphingolipid

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