Sterols are necessary for the growth of trypanosomatid protozoans; sterol biosynthesis is a potential target for the use and development of drugs to treat the diseases caused by these organisms. This study has used 14C-labelled substrates to investigate the carbon sources utilized by promastigotes and amastigotes of Leishmania mexicana for the production of sterol [mainly ergosta-5,7,24(241)-trien-3β-ol] and the fatty acid moieties of the triacylglycerol (TAG) and phospholipid (PL) of the organism. The isoprenoid precursor mevalonic acid (MVA) was incorporated into the sterols, and the sterol precursor squalene, by the promastigotes of L. mexicana. However, acetate (the precursor to MVA in most organisms) was a very poor substrate for sterol production but was readily incorporated into the fatty acids of TAG and PL. Other substrates (glucose, palmitic acid, alanine, serine and isoleucine), which are metabolized to acetyl-CoA, were also very poor precursors to sterol but were incorporated into TAG and PL and gave labelling patterns of the lipids similar to those of acetate. In contrast, the amino acid leucine was the only substrate to be incorporated efficiently into the squalene and sterol of L. mexicana promastigotes. Quantitative measurements revealed that at least 70-80% of the sterol synthesized by the promastigotes of L. mexicana is produced from carbon provided by leucine metabolism. Studies with the amastigote form of L. mexicana showed that in this case leucine was again the major sterol precursor, whereas acetate was utilized for fatty acid production.
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Research Article|
August 24 1999
Elucidation of carbon sources used for the biosynthesis of fatty acids and sterols in the trypanosomatid Leishmania mexicana
Michael L. GINGER;
Michael L. GINGER
1
*School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB, U.K.
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Michael L. CHANCE;
Michael L. CHANCE
†School of Tropical Medicine, University of Liverpool, Liverpool L3 5QA, U.K.
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L. John GOAD
L. John GOAD
2
*School of Biological Sciences, Life Sciences Building, University of Liverpool, Liverpool L69 7ZB, U.K.
2To whom correspondence should be addressed (ljgo@liv.ac.uk)
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Publisher: Portland Press Ltd
Received:
January 04 1999
Revision Received:
April 30 1999
Accepted:
June 21 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 342 (2): 397–405.
Article history
Received:
January 04 1999
Revision Received:
April 30 1999
Accepted:
June 21 1999
Citation
Michael L. GINGER, Michael L. CHANCE, L. John GOAD; Elucidation of carbon sources used for the biosynthesis of fatty acids and sterols in the trypanosomatid Leishmania mexicana. Biochem J 1 September 1999; 342 (2): 397–405. doi: https://doi.org/10.1042/bj3420397
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