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J Biol Chem. 2018 Nov 9;293(45):17308-17316. doi: 10.1074/jbc.R118.003213. Epub 2018 Oct 4.

Role of phospholipid synthesis in the development and differentiation of malaria parasites in the blood.

Author information

1
From the Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut 06520 and.
2
the Basic Science Section, Department of Medicine, National Jewish Health, Denver, Colorado 80206.
3
From the Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut 06520 and choukri.benmamoun@yale.edu.

Abstract

The life cycle of malaria parasites in both their mammalian host and mosquito vector consists of multiple developmental stages that ensure proper replication and progeny survival. The transition between these stages is fueled by nutrients scavenged from the host and fed into specialized metabolic pathways of the parasite. One such pathway is used by Plasmodium falciparum, which causes the most severe form of human malaria, to synthesize its major phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Much is known about the enzymes involved in the synthesis of these phospholipids, and recent advances in genetic engineering, single-cell RNA-Seq analyses, and drug screening have provided new perspectives on the importance of some of these enzymes in parasite development and sexual differentiation and have identified targets for the development of new antimalarial drugs. This Minireview focuses on two phospholipid biosynthesis enzymes of P. falciparum that catalyze phosphoethanolamine transmethylation (PfPMT) and phosphatidylserine decarboxylation (PfPSD) during the blood stages of the parasite. We also discuss our current understanding of the biochemical, structural, and biological functions of these enzymes and highlight efforts to use them as antimalarial drug targets.

KEYWORDS:

development; differentiation; malaria; phospholipid metabolism; plasmodium

PMID:
30287688
PMCID:
PMC6231132
[Available on 2019-11-09]
DOI:
10.1074/jbc.R118.003213
[Indexed for MEDLINE]

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