Metabolome analysis revealed increase in S-methylcysteine and phosphatidylisopropanolamine synthesis upon L-cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica

Afzal Husain, Dan Sato, Ghulam Jeelani, Fumika Mi-ichi, Vahab Ali, Makoto Suematsu, Tomoyoshi Soga, Tomoyoshi Nozaki

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)39160-39170
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number50
DOIs
Publication statusPublished - 2010 Dec 10

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Entamoeba histolytica
Metabolome
Cysteine
Parasites
Oxidative stress
Glycolysis
Sulfur
Amino Acids
Metabolism
Phospholipids
Oxidative Stress
S-methylcysteine
Cysteine Synthase
Pyruvaldehyde
S-Adenosylmethionine
Amebiasis
Capillary electrophoresis
Biological Models
Acetyl Coenzyme A
Cystine

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Metabolome analysis revealed increase in S-methylcysteine and phosphatidylisopropanolamine synthesis upon L-cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica. / Husain, Afzal; Sato, Dan; Jeelani, Ghulam; Mi-ichi, Fumika; Ali, Vahab; Suematsu, Makoto; Soga, Tomoyoshi; Nozaki, Tomoyoshi.

In: Journal of Biological Chemistry, Vol. 285, No. 50, 10.12.2010, p. 39160-39170.

Research output: Contribution to journalArticle

Husain, Afzal ; Sato, Dan ; Jeelani, Ghulam ; Mi-ichi, Fumika ; Ali, Vahab ; Suematsu, Makoto ; Soga, Tomoyoshi ; Nozaki, Tomoyoshi. / Metabolome analysis revealed increase in S-methylcysteine and phosphatidylisopropanolamine synthesis upon L-cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 50. pp. 39160-39170.
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