Novel sterol metabolic network of Trypanosoma brucei procyclic and bloodstream forms

Biochem J. 2012 Apr 1;443(1):267-77. doi: 10.1042/BJ20111849.


Trypanosoma brucei is the protozoan parasite that causes African trypanosomiasis, a neglected disease of people and animals. Co-metabolite analysis, labelling studies using [methyl-2H3]-methionine and substrate/product specificities of the cloned 24-SMT (sterol C24-methyltransferase) and 14-SDM (sterol C14demethylase) from T. brucei afforded an uncommon sterol metabolic network that proceeds from lanosterol and 31-norlanosterol to ETO [ergosta-5,7,25(27)-trien-3β-ol], 24-DTO [dimethyl ergosta-5,7,25(27)-trienol] and ergosterol [ergosta-5,7,22(23)-trienol]. To assess the possible carbon sources of ergosterol biosynthesis, specifically 13C-labelled specimens of lanosterol, acetate, leucine and glucose were administered to T. brucei and the 13C distributions found were in accord with the operation of the acetate-mevalonate pathway, with leucine as an alternative precursor, to ergostenols in either the insect or bloodstream form. In searching for metabolic signatures of procyclic cells, we observed that the 13C-labelling treatments induce fluctuations between the acetyl-CoA (mitochondrial) and sterol (cytosolic) synthetic pathways detected by the progressive increase in 13C-ergosterol production (control<[2-(13)C]leucine<[2-(13)C]acetate<[1-(13)C]glucose) and corresponding depletion of cholesta-5,7,24-trienol. We conclude that anabolic fluxes originating in mitochondrial metabolism constitute a flexible part of sterol synthesis that is further fluctuated in the cytosol, yielding distinct sterol profiles in relation to cell demands on growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Escherichia coli
  • Metabolome
  • Methyltransferases / biosynthesis
  • Methyltransferases / chemistry
  • Protozoan Proteins / biosynthesis
  • Protozoan Proteins / chemistry
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Sterol 14-Demethylase / biosynthesis
  • Sterol 14-Demethylase / chemistry
  • Sterols / biosynthesis*
  • Sterols / chemistry
  • Sterols / metabolism
  • Trypanosoma brucei brucei / metabolism
  • Trypanosoma brucei brucei / physiology*


  • Protozoan Proteins
  • Recombinant Proteins
  • Sterols
  • Sterol 14-Demethylase
  • Methyltransferases