Document Detail


Toxoplasma gondii acyl-lipid metabolism: de novo synthesis from apicoplast-generated fatty acids versus scavenging of host cell precursors.
MedLine Citation:
PMID:  16246004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Toxoplasma gondii is an obligate intracellular parasite that contains a relic plastid, called the apicoplast, deriving from a secondary endosymbiosis with an ancestral alga. Metabolic labelling experiments using [14C]acetate led to a substantial production of numerous glycero- and sphingo-lipid classes in extracellular tachyzoites. Syntheses of all these lipids were affected by the herbicide haloxyfop, demonstrating that their de novo syntheses necessarily required a functional apicoplast fatty acid synthase II. The complex metabolic profiles obtained and a census of glycerolipid metabolism gene candidates indicate that synthesis is probably scattered in the apicoplast membranes [possibly for PA (phosphatidic acid), DGDG (digalactosyldiacylglycerol) and PG (phosphatidylglycerol)], the endoplasmic reticulum (for major phospholipid classes and ceramides) and mitochondria (for PA, PG and cardiolipid). Based on a bioinformatic analysis, it is proposed that apicoplast produced acyl-ACP (where ACP is acyl-carrier protein) is transferred to glycerol-3-phosphate for apicoplast glycerolipid synthesis. Acyl-ACP is also probably transported outside the apicoplast stroma and irreversibly converted into acyl-CoA. In the endoplasmic reticulum, acyl-CoA may not be transferred to a three-carbon backbone by an enzyme similar to the cytosolic plant glycerol-3-phosphate acyltransferase, but rather by a dual glycerol-3-phosphate/dihydroxyacetone-3-phosphate acyltransferase like in animal and yeast cells. We further showed that intracellular parasites could also synthesize most of their lipids from scavenged host cell precursors. The observed appearance of glycerolipids specific to either the de novo pathway in extracellular parasites (unknown glycerolipid 1 and the plant like DGDG), or the intracellular stages (unknown glycerolipid 8), may explain the necessary coexistence of both de novo parasitic acyl-lipid synthesis and recycling of host cell compounds.
Authors:
Cordelia Bisanz; Olivier Bastien; Delphine Grando; Juliette Jouhet; Eric Maréchal; Marie-France Cesbron-Delauw
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  394     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-26     Completed Date:  2006-03-24     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  197-205     Citation Subset:  IM    
Affiliation:
Laboratoire Adaptation et Pathogénie des Micro-organismes, UMR 5163, CNRS-UJF, Grenoble, France. cordelia.bisanz@ujf-grenoble.fr
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MeSH Terms
Descriptor/Qualifier:
Acetyltransferases / genetics,  metabolism
Animals
Arabidopsis / genetics
Fatty Acid Synthetase Complex, Type II
Fatty Acids / biosynthesis,  metabolism*
Fibroblasts / metabolism*,  parasitology*
Gene Deletion
Gene Expression Regulation, Enzymologic
Host-Parasite Interactions
Humans
Intracellular Membranes / metabolism
Lipid Metabolism*
Lipids / biosynthesis*
Multienzyme Complexes / genetics,  metabolism
Sphingolipids / biosynthesis
Toxoplasma / enzymology,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
AI05093/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Lipids; 0/Multienzyme Complexes; 0/Sphingolipids; EC 2.3.1.-/Acetyltransferases; EC 6.-/Fatty Acid Synthetase Complex, Type II
Comments/Corrections

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