Phospholipid metabolism of serine in <i>Plasmodium</i>-infected erythrocytes involves phosphatidylserine and direct serine decarboxylation

Erythrocytes lack nuclei and mitochondria, the organelles important for apoptosis of nucleated cells. However, following increase of cytosolic Ca 2 þ activity, erythrocytes undergo cell shrinkage, cell membrane blebbing and breakdown of phosphatidylserine asymmetry, all features typical for apoptosis in nucleated cells. The same events are observed following osmotic shock, an effect mediated in part by activation of Ca 2 þ -permeable cation channels. However, erythrocyte death following osmotic shock is blunted but not prevented in the absence of extracellular Ca 2 þ pointing to additional mechanisms. As shown in this study, osmotic shock (950 mOsm) triggers sphingomyelin breakdown and formation of ceramide. The stimulation of annexin binding following osmotic shock is mimicked by addition of ceramide or purified sphingomyelinase and significantly blunted by genetic (aSM-deficient mice) or pharmacologic (50 lM 3,4-dichloroisocoumarin) knockout of sphingomyelinase. The effect of ceramide is blunted but not abolished in the absence of Ca 2 þ . Conversely, osmotic shock-induced annexin binding is potentiated in the presence of sublethal concentrations of ceramide. In conclusion, ceramide and Ca 2 þ entry through cation channels concert to trigger erythrocyte death during osmotic shock.

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“…22 To test for sphingomyelin breakdown, we labeled erythrocytes with radioactive choline and measured the incorporation of [methyl-…”

Section: Osmotic Shock Induces Sphingomyelin Breakdownmentioning

confidence: 99%

Involvement of ceramide in hyperosmotic shock-induced death of erythrocytes

et al. 2003

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“…1). In the serine decarboxylase-CDP-ethanolamine pathway, serine is decarboxylated by a parasite-specific serine decarboxylase (PfSD) to form ethanolamine (Etn) (7,8). Serine decarboxylation is unique to malarial parasites and plants (9).…”

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confidence: 99%

Identification of Gene Encoding Plasmodium knowlesi Phosphatidylserine Decarboxylase by Genetic Complementation in Yeast and Characterization of in Vitro Maturation of Encoded Enzyme

Choi

Augagneur

Mamoun

et al. 2012

Journal of Biological Chemistry

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Background: Functional screening of malaria (P. falciparum) genes is a problem because of A ϩ T content. Results: Use of a P. knowlesi cDNA library and a yeast mutant identifies an important parasite cDNA/gene and reveals new regulation of lipid synthesis. Conclusion:The P. knowlesi library will enable extrapolation to P. falciparum. Significance: Functional screening of malaria genes is now greatly enhanced.

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“…SDC has not been definitively demonstrated in any organism, although there is circumstantial evidence for its presence in malarial parasites, Plasmodium spp. (15).…”

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confidence: 99%

Plants Synthesize Ethanolamine by Direct Decarboxylation of Serine Using a Pyridoxal Phosphate Enzyme

Rontein

Nishida

Tashiro

et al. 2001

Journal of Biological Chemistry

135

124

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The established pathways from serine to ethanolamine are indirect and involve decarboxylation of phosphatidylserine. Here we show that plants can decarboxylate serine directly. Using a radioassay based on ethanolamine (Etn) formation, pyridoxal 5-phosphatedependent L-serine decarboxylase (SDC) activity was readily detected in soluble extracts from leaves of diverse species, including spinach, Arabidopsis, and rapeseed. A putative Arabidopsis SDC cDNA was identified by searching GenBank TM for sequences homologous to other amino acid decarboxylases and shown by expression in Escherichia coli to encode a soluble protein with SDC activity. This cDNA was further authenticated by complementing the Etn requirement of a yeast psd1 psd2 mutant. In a parallel approach, a cDNA was isolated from a rapeseed library by its ability to complement the Etn requirement of a yeast cho1 mutant and shown by expression in E. coli to specify SDC. The deduced Arabidopsis and rapeseed SDC polypeptides are 90% identical, lack obvious targeting signals, and belong to amino acid decarboxylase group II. Recombinant Arabidopsis SDC was shown to exist as a tetramer and to contain pyridoxal 5-phosphate. It does not attack D-serine, L-phosphoserine, other L-amino acids, or phosphatidylserine and is not inhibited by Etn, choline, or their phosphoesters. As a soluble, pyridoxal 5-phosphate enzyme, SDC contrasts sharply with phosphatidylserine decarboxylases, which are membrane proteins that have a pyruvoyl cofactor.

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Phospholipid metabolism of serine in Plasmodium-infected erythrocytes involves phosphatidylserine and direct serine decarboxylation

Cited by 69 publications

References 43 publications

Involvement of ceramide in hyperosmotic shock-induced death of erythrocytes

Involvement of ceramide in hyperosmotic shock-induced death of erythrocytes

Identification of Gene Encoding Plasmodium knowlesi Phosphatidylserine Decarboxylase by Genetic Complementation in Yeast and Characterization of in Vitro Maturation of Encoded Enzyme

Plants Synthesize Ethanolamine by Direct Decarboxylation of Serine Using a Pyridoxal Phosphate Enzyme

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