Glyceroneogenesis: an unexpected metabolic pathway for glutamine in Schistosoma mansoni sporocysts.
To date, glyceroneogenesis has only been described in mammals but we demonstrate in this paper that it could exist in the invertebrate Schistosoma mansoni, the parasitic helminth transmitted by fresh water molluscs and responsible for the major human endemic disease, schistosomiasis. Glyceroneogenesis is a phosphoenolpyruvate carboxykinase (PEPCK)-dependent process by which glycerol can be produced from precursors like glutamine and therefore represents a truncated gluconeogenic pathway. We have previously demonstrated the possible central role of glutamine in mollusc-schistosome interactions. In this work, we show that glutamine effectively promotes in vitro survival and protein synthesis in sporocysts, the intramolluscan larval stages of S. mansoni, possibly through its role as an energy source. However, the demonstration that PEPCK is massively expressed in these larval forms as compared to adult parasites, together with the observation that 3-mercaptopicolinate, a specific inhibitor of PEPCK, significantly reduces the effect of glutamine on sporocyst growth, suggest that glutamine could also be used for glucose or glycerol production. Results of [14C] glutamine incorporation confirmed that neosynthesis of glucose and mainly of glycerol occurred in sporocysts and was dependent on PEPCK activity. Therefore, our results strongly indicate that glyceroneogenesis could exist in schistosomes. Several hypotheses can be proposed concerning the importance of glycerol for the adaptation of this helminth to its host osmotic and energetic environment.
Khayath
Naji
N
U547 INSERM, Institut Pasteur de Lille, 1 rue du Pr. Calmette, 59019 Lille Cedex, France.
Mithieux
Gilles
G
Zitoun
Carine
C
Coustau
Christine
C
Vicogne
Jérôme
J
Tielens
Aloysius G
AG
Dissous
Colette
C
D000818:Animals; D001700:Biomphalaria / Q000469:parasitology; D006224:Cricetinae; D003470:Culture Media; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism*; D006790:Host-Parasite Interactions; D008647:Mesocricetus / Q000469:parasitology; D033661:Oocysts / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D012550:Schistosoma mansoni / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*
D003470:Culture Media; D005973:Glutamine; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose; D005990:Glycerol