TY - JOUR
T1 - Fatty Acid Synthesis by Elongases in Trypanosomes
AU - Lee, Soo Hee
AU - Stephens, Jennifer L.
AU - Paul, Kimberly S.
AU - Englund, Paul T.
N1 - Funding Information:
We thank Steve Beverly, Teresa Dunn, Dennis Grab, Dan Lane, Yasu Morita, Shilpi Paul, Terry Shapiro, and Paul Watkins for discussions. We thank Barbara Burleigh and Anne Chessler for T. cruzi lysates and Dennis Dwyer for L. major cells and media. We thank Gokben Yildirir for technical assistance and members of our laboratory for support. We thank Wade Gibson for use of the phosphorimager. This work was supported by a grant from the National Institutes of Health (AI21334).
PY - 2006/8/25
Y1 - 2006/8/25
N2 - All eukaryotic and prokaryotic organisms are thought to synthesize fatty acids using a type I or type II synthase. In addition, eukaryotes extend pre-existing long chain fatty acids using microsomal elongases (ELOs). We have found that Trypanosoma brucei, a eukaryotic human parasite that causes sleeping sickness, uses three elongases instead of type I or type II synthases for the synthesis of nearly all its fatty acids. Trypanosomes encounter diverse environments during their life cycle with different fatty acid requirements. The tsetse vector form requires synthesis of stearate (C18), whereas the bloodstream form needs myristate (C14). We find that trypanosome fatty acid synthesis is modular, with ELO1 converting C4 to C10, ELO2 extending C10 to C14, and ELO3 elongating C14 to C18. In blood, ELO3 downregulation favors myristate synthesis, whereas low concentrations of exogenous fatty acids in cultured parasites cause upregulation of the entire pathway, allowing the parasite to adapt to different environments.
AB - All eukaryotic and prokaryotic organisms are thought to synthesize fatty acids using a type I or type II synthase. In addition, eukaryotes extend pre-existing long chain fatty acids using microsomal elongases (ELOs). We have found that Trypanosoma brucei, a eukaryotic human parasite that causes sleeping sickness, uses three elongases instead of type I or type II synthases for the synthesis of nearly all its fatty acids. Trypanosomes encounter diverse environments during their life cycle with different fatty acid requirements. The tsetse vector form requires synthesis of stearate (C18), whereas the bloodstream form needs myristate (C14). We find that trypanosome fatty acid synthesis is modular, with ELO1 converting C4 to C10, ELO2 extending C10 to C14, and ELO3 elongating C14 to C18. In blood, ELO3 downregulation favors myristate synthesis, whereas low concentrations of exogenous fatty acids in cultured parasites cause upregulation of the entire pathway, allowing the parasite to adapt to different environments.
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U2 - 10.1016/j.cell.2006.06.045
DO - 10.1016/j.cell.2006.06.045
M3 - Article
C2 - 16923389
AN - SCOPUS:33747154470
VL - 126
SP - 691
EP - 699
JO - Cell
JF - Cell
SN - 0092-8674
IS - 4
ER -