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Exploring metabolomic approaches to analyse phospholipid biosynthetic pathways in Plasmodium

Published online by Cambridge University Press:  29 January 2010

S. BESTEIRO ,
S. VO DUY ,
C. PERIGAUD ,
I. LEFEBVRE-TOURNIER  and
H. J. VIAL
S. BESTEIRO
Affiliation:
Dynamique des Interactions Membranaires Normales et Pathologiques, UMR 5235, Centre National de la Recherche Scientifique – UM1-UM2, Université Montpellier 2, cc 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France
S. VO DUY
Affiliation:
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Centre National de la Recherche Scientifique – UM1-UM2, Université Montpellier 2, cc 1705, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France
C. PERIGAUD
Affiliation:
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Centre National de la Recherche Scientifique – UM1-UM2, Université Montpellier 2, cc 1705, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France
I. LEFEBVRE-TOURNIER
Affiliation:
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Centre National de la Recherche Scientifique – UM1-UM2, Université Montpellier 2, cc 1705, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France
H. J. VIAL*
Affiliation:
Dynamique des Interactions Membranaires Normales et Pathologiques, UMR 5235, Centre National de la Recherche Scientifique – UM1-UM2, Université Montpellier 2, cc 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France
*
Corresponding author: Henri Vial, Dynamique des Interactions Membranaires Normales et Pathologiques, UMR 5235, Centre National de la Recherche Scientifique – UM1-UM2, Université Montpellier 2, cc 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France. Tel: +33 (0) 4 6714 3745, Fax: +33 (0) 4 6714 4286, E-mail: vial@univ-montp2.fr
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Summary

Plasmodium falciparum, the agent responsible for malaria, is an obligate intracellular protozoan parasite. For proliferation, differentiation and survival, it relies on its own protein-encoding genes, as well as its host cells for nutrient sources. Nutrients and subsequent metabolites are required by the parasites to support their high rate of growth and replication, particularly in the intra-erythrocytic stages of the parasite that are responsible for the clinical symptoms of the disease. Advances in mass spectrometry have improved the analysis of endogenous metabolites and enabled a global approach to identify the parasite's metabolites by the so-called metabolomic analyses. This level of analysis complements the genomic, transcriptomic and proteomic data already available and should allow the identification of novel metabolites, original pathways and networks of regulatory interactions within the parasite, and between the parasite and its hosts. The field of metabolomics is just in its infancy in P. falciparum, hence in this review, we concentrate on the available methodologies and their potential applications for deciphering important biochemical processes of the parasite, such as the astonishingly diverse phospholipid biosynthesis pathways. Elucidating the regulation of the biosynthesis of these crucial metabolites could help design of future anti-malarial drugs.

Keywords

PlasmodiummalariametabolomicsphospholipidsLC-MSmass spectrometry
Type
Research Article
Information
Parasitology , Volume 137 , Special Issue 9: Insights into the metabolomes of parasites , August 2010 , pp. 1343 - 1356
Copyright
Copyright © Cambridge University Press 2010

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References

REFERENCES

Alberge, B., Gannoun-Zaki, L., Bascunana, C., Tran Van Ba, C., Vial, H. and Cerdan, R. (2009). Comparison of the cellular and biochemical properties of Plasmodium falciparum choline and ethanolamine kinases. Biochemical Journal, October 21 [Epub ahead of print].Google ScholarPubMed
Aurrecoechea, C., Brestelli, J., Brunk, B. P., Dommer, J., Fischer, S., Gajria, B., Gao, X., Gingle, A., Grant, G., Harb, O. S., Heiges, M., Innamorato, F., Iodice, J., Kissinger, J. C., Kraemer, E., Li, W., Miller, J. A., Nayak, V., Pennington, C., Pinney, D. F., Roos, D. S., Ross, C., Stoeckert, C. J. Jr., Treatman, C. and Wang, H. (2009). PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Research 37, D539–543.Google Scholar
Bajad, S. U., Lu, W., Kimball, E. H., Yuan, J., Peterson, C. and Rabinowitz, J. D. (2006). Separation and quantitation of water soluble cellular metabolites by hydrophilic interaction chromatography-tandem mass spectrometry. Journal of Chromatography A 1125, 76–88.CrossRefGoogle ScholarPubMed
Baumeister, S., Paprotka, K., Bhakdi, S. and Lingelbach, K. (2001). Selective permeabilization of infected host cells with pore-forming proteins provides a novel tool to study protein synthesis and viability of the intracellular apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii. Molecular and Biochemical Parasitology 112, 133–137.CrossRefGoogle ScholarPubMed
Baunaure, F., Eldin, P., Cathiard, A. M. and Vial, H. (2004). Characterization of a non-mitochondrial type I phosphatidylserine decarboxylase in Plasmodium falciparum. Molecular Microbiology 51, 33–46.CrossRefGoogle ScholarPubMed
Biagini, G. A., Pasini, E. M., Hughes, R., De Koning, H. P., Vial, H. J., O'neill, P. M., Ward, S. A. and Bray, P. G. (2004). Characterization of the choline carrier of Plasmodium falciparum: a route for the selective delivery of novel antimalarial drugs. Blood 104, 3372–3377.CrossRefGoogle ScholarPubMed
Bolten, C. J., Kiefer, P., Letisse, F., Portais, J. C. and Wittmann, C. (2007). Sampling for metabolome analysis of microorganisms. Analytical Chemistry 79, 3843–3849.CrossRefGoogle ScholarPubMed
Carman, G. M. and Henry, S. A. (1989). Phospholipid biosynthesis in yeast. Annual Review of Biochemistry 58, 635–669.CrossRefGoogle ScholarPubMed
Caspi, R., Foerster, H., Fulcher, C. A., Kaipa, P., Krummenacker, M., Latendresse, M., Paley, S., Rhee, S. Y., Shearer, A. G., Tissier, C., Walk, T. C., Zhang, P. and Karp, P. D. (2008). The MetaCyc Database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases. Nucleic Acids Research 36, D623–631.CrossRefGoogle ScholarPubMed
Castro-Perez, J., Plumb, R., Granger, J. H., Beattie, I., Joncour, K. and Wright, A. (2005). Increasing throughput and information content for in vitro drug metabolism experiments using ultra-performance liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer. Rapid Communications in Mass Spectrometry 19, 843–848.CrossRefGoogle ScholarPubMed
Choubey, V., Guha, M., Maity, P., Kumar, S., Raghunandan, R., Maulik, P. R., Mitra, K., Halder, U. C. and Bandyopadhyay, U. (2006). Molecular characterization and localization of Plasmodium falciparum choline kinase. Biochimica et Biophysica Acta 1760, 1027–1038.CrossRefGoogle ScholarPubMed
Churchwell, M. I., Twaddle, N. C., Meeker, L. R. and Doerge, D. R. (2005). Improving LC-MS sensitivity through increases in chromatographic performance: comparisons of UPLC-ES/MS/MS to HPLC-ES/MS/MS. Journal of Chromatography B Analytical Technologies in the Biomedical and Life Sciences 825, 134–143.CrossRefGoogle ScholarPubMed
De Koning, W. and Van Dam, K. (1992). A method for the determination of changes of glycolytic metabolites in yeast on a subsecond time scale using extraction at neutral pH. Analytical Biochemistry 204, 118–123.CrossRefGoogle ScholarPubMed
Dechamps, S., Maynadier, M., Wein, S., Gannoun-Zaki, L., Marechal, E. and Vial, H. J. (2009). Rodent and non-rodent malaria parasites differ in their phospholipid metabolic pathways. Journal of Lipid Research, June 26 [Epub ahead of print].Google Scholar
Dowhan, W. (1997). Molecular basis for membrane phospholipid diversity: why are there so many lipids? Annual Review of Biochemistry 66, 199–232.CrossRefGoogle ScholarPubMed
Elabbadi, N., Ancelin, M. L. and Vial, H. J. (1997). Phospholipid metabolism of serine in Plasmodium-infected erythrocytes involves phosphatidylserine and direct serine decarboxylation. Biochemical Journal 324 (Pt 2), 435–445.CrossRefGoogle ScholarPubMed
Enjalbal, C., Roggero, R., Cerdan, R., Martinez, J., Vial, H. and Aubagnac, J. L. (2004). Automated monitoring of phosphatidylcholine biosyntheses in Plasmodium falciparum by electrospray ionization mass spectrometry through stable isotope labeling experiments. Analytical Chemistry 76, 4515–4521.CrossRefGoogle ScholarPubMed
Fatumo, S., Plaimas, K., Mallm, J. P., Schramm, G., Adebiyi, E., Oswald, M., Eils, R. and Konig, R. (2009). Estimating novel potential drug targets of Plasmodium falciparum by analysing the metabolic network of knock-out strains in silico. Infection, Genetics and Evolution 9, 351–358.CrossRefGoogle ScholarPubMed
Fiehn, O. (2002). Metabolomics – the link between genotypes and phenotypes. Plant Molecular Biology 48, 155–171.CrossRefGoogle ScholarPubMed
Gardner, M. J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R. W., Carlton, J. M., Pain, A., Nelson, K. E., Bowman, S., Paulsen, I. T., James, K., Eisen, J. A., Rutherford, K., Salzberg, S. L., Craig, A., Kyes, S., Chan, M. S., Nene, V., Shallom, S. J., Suh, B., Peterson, J., Angiuoli, S., Pertea, M., Allen, J., Selengut, J., Haft, D., Mather, M. W., Vaidya, A. B., Martin, D. M., Fairlamb, A. H., Fraunholz, M. J., Roos, D. S., Ralph, S. A., Mcfadden, G. I., Cummings, L. M., Subramanian, G. M., Mungall, C., Venter, J. C., Carucci, D. J., Hoffman, S. L., Newbold, C., Davis, R. W., Fraser, C. M. and Barrell, B. (2002). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498–511.CrossRefGoogle ScholarPubMed
Ginsburg, H. (2006). Progress in in silico functional genomics: the malaria Metabolic Pathways database. Trends in Parasitology 22, 238–240.CrossRefGoogle ScholarPubMed
Ginsburg, H. (2009). Caveat emptor: limitations of the automated reconstruction of metabolic pathways in Plasmodium. Trends in Parasitology 25, 37–43.CrossRefGoogle ScholarPubMed
Guo, Y. and Gaiki, S. (2005). Retention behavior of small polar compounds on polar stationary phases in hydrophilic interaction chromatography. Journal of Chromatography A 1074, 71–80.CrossRefGoogle ScholarPubMed
Holz, G. G. (1977). Lipids and the malaria parasite. Bulletin of the World Health Organization 55, 237–248.Google Scholar
Idborg-Bjorkman, H., Edlund, P. O., Kvalheim, O. M., Schuppe-Koistinen, I. and Jacobsson, S. P. (2003). Screening of biomarkers in rat urine using LC/electrospray ionization-MS and two-way data analysis. Analytical Chemistry 75, 4784–4792.CrossRefGoogle ScholarPubMed
Jackson, K. E., Spielmann, T., Hanssen, E., Adisa, A., Separovic, F., Dixon, M. W. A., Trenholme, K. R., Hawthorne, P. L., Gardiner, D. L., Gilberger, T. and Tilley, L. (2007). Selective permeabilization of the host cell membrane of Plasmodium falciparum-infected red blood cells with streptolysin O and equinatoxin II. Biochemical Journal 403, 167–175.CrossRefGoogle ScholarPubMed
Jin, Y., Xue, X., Shi, H., Xiao, Y., Zhang, F. and Liang, X. (2008). HPLC and UPLC Switch for TCM analysis. World Science and Technology 10, 80–84.CrossRefGoogle Scholar
Kanehisa, M., Araki, M., Goto, S., Hattori, M., Hirakawa, M., Itoh, M., Katayama, T., Kawashima, S., Okuda, S., Tokimatsu, T. and Yamanishi, Y. (2008). KEGG for linking genomes to life and the environment. Nucleic Acids Research 36, D480–484.CrossRefGoogle ScholarPubMed
Kent, C. (1995). Eukaryotic phospholipid biosynthesis. Annual Review of Biochemistry 64, 315–343.CrossRefGoogle ScholarPubMed
Lambros, C. and Vanderberg, J. P. (1979). Synchronization of Plasmodium falciparum erythrocytic stages in culture. Journal of Parasitology 65, 418–420.CrossRefGoogle ScholarPubMed
Le Roch, K. G., Johnson, J. R., Ahiboh, H., Chung, D. W., Prudhomme, J., Plouffe, D., Henson, K., Zhou, Y., Witola, W., Yates, J. R., Mamoun, C. B., Winzeler, E. A. and Vial, H. (2008). A systematic approach to understand the mechanism of action of the bisthiazolium compound T4 on the human malaria parasite, Plasmodium falciparum. BMC Genomics 9, 513.CrossRefGoogle ScholarPubMed
Lenz, E. M. and Wilson, I. D. (2007). Analytical strategies in metabonomics. Journal of Proteome Research 6, 443–458.CrossRefGoogle ScholarPubMed
Li, J. V., Wang, Y., Saric, J., Nicholson, J. K., Dirnhofer, S., Singer, B. H., Tanner, M., Wittlin, S., Holmes, E. and Utzinger, J. (2008). Global metabolic responses of NMRI mice to an experimental Plasmodium berghei infection. Journal of Proteome Research 7, 3948–3956.CrossRefGoogle Scholar
Li, Z. and Vance, D. E. (2008). Phosphatidylcholine and choline homeostasis. Journal of Lipid Research 49, 1187–1194.Google Scholar
Lian, L. Y., Al-Helal, M., Roslaini, A. M., Fisher, N., Bray, P. G., Ward, S. A. and Biagini, G. A. (2009). Glycerol: an unexpected major metabolite of energy metabolism by the human malaria parasite. Malaria Journal 8, 38.CrossRefGoogle ScholarPubMed
Lokhov, P. and Archakov, A. (2009). Mass spectrometry methods in metabolomics. Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry 3, 1–9.CrossRefGoogle Scholar
Maier, A. G., Cooke, B. M., Cowman, A. F. and Tilley, L. (2009). Malaria parasite proteins that remodel the host erythrocyte. Nature Reviews Microbiology 7, 341–354.CrossRefGoogle ScholarPubMed
Martin, D., Gannoun-Zaki, L., Bonnefoy, S., Eldin, P., Wengelnik, K. and Vial, H. (2000). Characterization of Plasmodium falciparum CDP-diacylglycerol synthase, a proteolytically cleaved enzyme. Molecular and Biochemical Parasitology 110, 93–105.Google Scholar
Massou, S., Nicolas, C., Letisse, F. and Portais, J. C. (2007). NMR-based fluxomics: quantitative 2D NMR methods for isotopomers analysis. Phytochemistry 68, 2330–2340.CrossRefGoogle ScholarPubMed
Matthews, L., Gopinath, G., Gillespie, M., Caudy, M., Croft, D., De Bono, B., Garapati, P., Hemish, J., Hermjakob, H., Jassal, B., Kanapin, A., Lewis, S., Mahajan, S., May, B., Schmidt, E., Vastrik, I., Wu, G., Birney, E., Stein, L. and D'eustachio, P. (2009). Reactome knowledgebase of human biological pathways and processes. Nucleic Acids Research 37, D619–622.CrossRefGoogle ScholarPubMed
Moll, G. N., Vial, H. J., Ancelin, M. L., Op Den Kamp, J. A., Roelofsen, B. and Van Deenen, L. L. (1988). Phospholipid uptake by Plasmodium knowlesi infected erythrocytes. FEBS Letters 232, 341–346.CrossRefGoogle ScholarPubMed
Naidong, W. (2003). Bioanalytical liquid chromatography tandem mass spectrometry methods on underivatized silica columns with aqueous/organic mobile phases. Journal of Chromatography B Analytical Technologies in the Biomedical and Life Sciences 796, 209–224.CrossRefGoogle ScholarPubMed
Olszewski, K. L., Morrisey, J. M., Wilinski, D., Burns, J. M., Vaidya, A. B., Rabinowitz, J. D. and Llinas, M. (2009). Host-parasite interactions revealed by Plasmodium falciparum metabolomics. Cell Host & Microbe 5, 191–199.CrossRefGoogle ScholarPubMed
Paul, F., Roath, S., Melville, D., Warhurst, D. C. and Osisanya, J. O. (1981). Separation of malaria-infected erythrocytes from whole blood: use of a selective high-gradient magnetic separation technique. Lancet 2, 70–71.Google Scholar
Pessi, G., Choi, J. Y., Reynolds, J. M., Voelker, D. R. and Mamoun, C. B. (2005). In vivo evidence for the specificity of Plasmodium falciparum phosphoethanolamine methyltransferase and its coupling to the Kennedy pathway. Journal of Biological Chemistry 280, 12461–12466.CrossRefGoogle Scholar
Pessi, G., Kociubinski, G. and Mamoun, C. B. (2004). A pathway for phosphatidylcholine biosynthesis in Plasmodium falciparum involving phosphoethanolamine methylation. Proceedings of the National Academy of Sciences, USA 101, 6206–6211.Google Scholar
Pharkya, P., Nikolaev, E. V. and Maranas, C. D. (2003). Review of the BRENDA Database. Metabolic Engineering 5, 71–73.CrossRefGoogle ScholarPubMed
Pinney, J. W., Papp, B., Hyland, C., Wambua, L., Westhead, D. R. and Mcconkey, G. A. (2007). Metabolic reconstruction and analysis for parasite genomes. Trends in Parasitology 23, 548–554.CrossRefGoogle ScholarPubMed
Plumb, R., Castro-Perez, J., Granger, J., Beattie, I., Joncour, K. and Wright, A. (2004). Ultra-performance liquid chromatography coupled to quadrupole-orthogonal time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 18, 2331–2337.CrossRefGoogle ScholarPubMed
Rontein, D., Nishida, I., Tashiro, G., Yoshioka, K., Wu, W. I., Voelker, D. R., Basset, G. and Hanson, A. D. (2001). Plants synthesize ethanolamine by direct decarboxylation of serine using a pyridoxal phosphate enzyme. Journal of Biological Chemistry 276, 35523–35529.CrossRefGoogle ScholarPubMed
Teng, R., Junankar, P. R., Bubb, W. A., Rae, C., Mercier, P. and Kirk, K. (2009). Metabolite profiling of the intraerythrocytic malaria parasite Plasmodium falciparum by (1)H NMR spectroscopy. NMR in Biomedicine 22, 292–302.CrossRefGoogle ScholarPubMed
Trager, W. and Jensen, J. B. (1976). Human malaria parasites in continuous culture. Science 193, 673–675.CrossRefGoogle ScholarPubMed
Trager, W. and Williams, J. (1992). Extracellular (axenic) development in vitro of the erythrocytic cycle of Plasmodium falciparum. Proceedings of the National Academy of Sciences, USA 89, 5351–5355.CrossRefGoogle ScholarPubMed
Trager, W., Zung, J. and Tershakovec, M. (1990). Initial extracellular development in vitro of erythrocytic stages of malaria parasites (Plasmodium falciparum). Proceedings of the National Academy of Sciences, USA 87, 5618–5622.CrossRefGoogle ScholarPubMed
Van Brummelen, A. C., Olszewski, K. L., Wilinski, D., Llinas, M., Louw, A. I. and Birkholtz, L. M. (2009). Co-inhibition of Plasmodium falciparum S-adenosylmethionine decarboxylase/ornithine decarboxylase reveals perturbation-specific compensatory mechanisms by transcriptome, proteome, and metabolome analyses. Journal of Biological Chemistry 284, 4635–4646.CrossRefGoogle ScholarPubMed
Van De Steene, J. C. and Lambert, W. E. (2008). Comparison of matrix effects in HPLC-MS/MS and UPLC-MS/MS analysis of nine basic pharmaceuticals in surface waters. Journal of the American Society for Mass Spectrometry 19, 713–718.CrossRefGoogle ScholarPubMed
Vial, H. and Ancelin, M. (1998). Malarial Lipids. In Malaria: Parasite Biology, Biogenesis, Protection (ed. Sherman, I.), pp. 159–175. ASM Press, Washington DC.Google Scholar
Vial, H. J. and Ancelin, M. L. (1992). Malarial lipids. An overview. Subcellular Biochemistry 18, 259–306.CrossRefGoogle ScholarPubMed
Vial, H. J., Ancelin, M. L., Philippot, J. R. and Thuet, M. J. (1990). Biosynthesis and dynamics of lipids in Plasmodium-infected mature mammalian erythrocytes. Blood Cells 16, 531–555.Google ScholarPubMed
Vial, H. J. and Calas, M. (2001). Inhibitors of Phospholipid Metabolism. In Antimalarial Chemotherapy, Mechanisms of Action, Modes of Resistance, and New Directions in Drug Development (ed. Rosenthal, P.), pp. 347–365. Humana Press, Totowa, NJ.Google Scholar
Vial, H. and Mamoun, C. (2005). Plasmodium Lipids: Metabolism and Function. In Molecular Approach to Malaria (ed. Sherman, I.), pp. 327–352. ASM Press, Washington DC.Google Scholar
Vial, H. J., Thuet, M. J., Broussal, J. L. and Philippot, J. R. (1982). Phospholipid biosynthesis by Plasmodium knowlesi-infected erythrocytes: the incorporation of phospohlipid precursors and the identification of previously undetected metabolic pathways. Journal of Parasitology 68, 379–391.CrossRefGoogle ScholarPubMed
Vial, H. J., Thuet, M. J. and Philippot, J. R. (1984). Cholinephosphotransferase and ethanolaminephosphotransferase activities in Plasmodium knowlesi-infected erythrocytes. Their use as parasite-specific markers. Biochimica et Biophysica Acta 795, 372–383.CrossRefGoogle ScholarPubMed
Vial, H. J., Wein, S., Farenc, C., Kocken, C., Nicolas, O., Ancelin, M. L., Bressolle, F., Thomas, A. and Calas, M. (2004). Prodrugs of bisthiazolium salts are orally potent antimalarials. Proceedings of the National Academy of Sciences, USA 101, 15458–15463.CrossRefGoogle ScholarPubMed
Villas-Boas, S. G. and Bruheim, P. (2007). Cold glycerol-saline: the promising quenching solution for accurate intracellular metabolite analysis of microbial cells. Analytical Biochemistry 370, 87–97.CrossRefGoogle ScholarPubMed
Wengelnik, K. and Vial, H. J. (2007). Characterisation of the phosphatidylinositol synthase gene of Plasmodium species. Research in Microbiology 158, 51–59.CrossRefGoogle ScholarPubMed
Wengelnik, K., Vidal, V., Ancelin, M. L., Cathiard, A. M., Morgat, J. L., Kocken, C. H., Calas, M., Herrera, S., Thomas, A. W. and Vial, H. J. (2002). A class of potent antimalarials and their specific accumulation in infected erythrocytes. Science 295, 1311–1314.CrossRefGoogle ScholarPubMed
Whitaker, J. W., Letunic, I., McConkey, G. A. and Westhead, D. R. (2009). metaTIGER: a metabolic evolution resource. Nucleic Acids Research 37, D531–538.CrossRefGoogle ScholarPubMed
Wilson, I. D., Nicholson, J. K., Castro-Perez, J., Granger, J. H., Johnson, K. A., Smith, B. W. and Plumb, R. S. (2005 a). High resolution “ultra performance” liquid chromatography coupled to oa-TOF mass spectrometry as a tool for differential metabolic pathway profiling in functional genomic studies. Journal of Proteome Research 4, 591–598.CrossRefGoogle ScholarPubMed
Wilson, I. D., Plumb, R., Granger, J., Major, H., Williams, R. and Lenz, E. M. (2005 b). HPLC-MS-based methods for the study of metabonomics. Journal of Chromatography B Analytical Technologies in the Biomedical and Life Sciences 817, 67–76.CrossRefGoogle Scholar
Wishart, D. S. (2008). Quantitative metabolomics using NMR. TrAC Trends in Analytical Chemistry 27, 228–237.CrossRefGoogle Scholar
Witola, W. H., El Bissati, K., Pessi, G., Xie, C., Roepe, P. D. and Mamoun, C. B. (2008). Disruption of the Plasmodium falciparum PfPMT gene results in a complete loss of phosphatidylcholine biosynthesis via the serine-decarboxylase-phosphoethanolamine-methyltransferase pathway and severe growth and survival defects. Journal of Biological Chemistry 283, 27636–27643.CrossRefGoogle Scholar
Witola, W. H., Pessi, G., El Bissati, K., Reynolds, J. M. and Mamoun, C. B. (2006). Localization of the phosphoethanolamine methyltransferase of the human malaria parasite Plasmodium falciparum to the Golgi apparatus. Journal of Biological Chemistry 281, 21305–21311.Google Scholar
Yeh, I., Hanekamp, T., Tsoka, S., Karp, P. D. and Altman, R. B. (2004). Computational analysis of Plasmodium falciparum metabolism: organizing genomic information to facilitate drug discovery. Genome Research 14, 917–924.CrossRefGoogle ScholarPubMed
Zhang, Y. M. and Rock, C. O. (2008). Membrane lipid homeostasis in bacteria. Nature Reviews Microbiology 6, 222–233.Google Scholar