| Metabolome analysis revealed increase in S-methylcysteine and phosphatidylisopropanolamine synthesis upon L-cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica. | |
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MedLine Citation:
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PMID: 20923776 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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L-cysteine is ubiquitous in all living organisms and is involved in a variety of functions, including the synthesis of iron-sulfur clusters and glutathione and the regulation of the structure, stability, and catalysis of proteins. In the protozoan parasite Entamoeba histolytica, the causative agent of amebiasis, L-cysteine plays an essential role in proliferation, adherence, and defense against oxidative stress; however, the essentiality of this amino acid in the pathways it regulates is not well understood. In the present study, we applied capillary electrophoresis time-of-flight mass spectrometry to quantitate charged metabolites modulated in response to L-cysteine deprivation in E. histolytica, which was selected as a model for examining the biological roles of L-cysteine. L-cysteine deprivation had profound effects on glycolysis, amino acid, and phospholipid metabolism, with sharp decreases in the levels of L-cysteine, L-cystine, and S-adenosylmethionine and a dramatic accumulation of O-acetylserine and S-methylcysteine. We further demonstrated that S-methylcysteine is synthesized from methanethiol and O-acetylserine by cysteine synthase, which was previously considered to be involved in sulfur-assimilatory L-cysteine biosynthesis. In addition, L-cysteine depletion repressed glycolysis and energy generation, as it reduced acetyl-CoA, ethanol, and the major nucleotide di- and triphosphates, and led to the accumulation of glycolytic intermediates. Interestingly, L-cysteine depletion increased the synthesis of isopropanolamine and phosphatidylisopropanolamine, and it was confirmed that their increment was not a result of oxidative stress but was a specific response to L-cysteine depletion. We also identified a pathway in which isopropanolamine is synthesized from methylglyoxal via aminoacetone. To date, this study represents the first case where L-cysteine deprivation leads to drastic changes in core metabolic pathways, including energy, amino acid, and phospholipid metabolism. |
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Authors:
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Afzal Husain; Dan Sato; Ghulam Jeelani; Fumika Mi-ichi; Vahab Ali; Makoto Suematsu; Tomoyoshi Soga; Tomoyoshi Nozaki |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-05 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-06 Completed Date: 2011-01-10 Revised Date: 2011-12-13 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 39160-70 Citation Subset: IM |
Affiliation:
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Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Chromatography, Thin Layer Cysteine / analogs & derivatives*, chemistry* Cysteine Synthase / metabolism Entamoeba histolytica / metabolism* Gene Expression Regulation Glycolysis Kinetics Metabolomics / methods Oxidative Stress Propanolamines / chemistry* S-Adenosylmethionine / metabolism Serine / analogs & derivatives, chemistry |
| Chemical | |
Reg. No./Substance:
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0/Propanolamines; 29908-03-0/S-Adenosylmethionine; 4985-36-8/O-acetylserine; 52-90-4/Cysteine; 56-45-1/Serine; 7728-98-5/S-methylcysteine; 78-96-6/monoisopropanolamine; EC 2.5.1.47/Cysteine Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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