| The apicoplast and endoplasmic reticulum cooperate in fatty acid biosynthesis in the apicomplexan parasite Toxoplasma gondii. | |
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MedLine Citation:
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PMID: 22179608 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Apicomplexan parasites are responsible for high impact human diseases such as malaria, toxoplasmosis and cryptosporidiosis. These obligate intracellular pathogens are dependent on both de novo lipid biosynthesis as well as the uptake of host lipids for biogenesis of parasite membranes. Genome annotations and biochemical studies indicate that apicomplexan parasites can synthesize fatty acids via a number of different biosynthetic pathways that are differentially compartmentalized. However, the relative contribution of each of these biosynthetic pathways to total fatty acid composition of intracellular parasite stages remains poorly defined. Here we use a combination of genetic, biochemical and metabolomic approaches to delineate the contribution of fatty acid biosynthetic pathways in Toxoplasma gondii. Metabolic labeling studies with (13)Parasite fatty acid synthesis is an attractive drug target but complex and poorly understood.C-glucose showed that intracellular tachyzoites synthesized a range of long and very long chain fatty acids (C14:0-26:1). Genetic disruption of the apicoplast localized type II fatty acid synthase (FASII) resulted in greatly reduced synthesis of saturated fatty acids up to eighteen carbons long. Ablation of FASII activity resulted in reduced intracellular growth that was partially restored by addition of long chain fatty acids. In contrast, synthesis of very long chain fatty acids was primarily dependent on a fatty acid elongation system comprising three elongases, two reductases and a dehydratase that were localized to the endoplasmic reticulum. The function of these enzymes was confirmed by heterologous expression in yeast. This elongase pathway appears to have a unique role in generating very long unsaturated fatty acids (C26:1) that cannot be salvaged from the host. |
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Authors:
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Srinivasan Ramakrishnan; Melissa D Docampo; James I Macrae; François M Pujol; Carrie F Brooks; Giel G van Dooren; J Kalvero Hiltunen; Alexander J Kastaniotis; Malcolm J McConville; Boris Striepen |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-16 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Georgia, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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