Abstract
The general paradigm that emerges from the analysis of the transcriptome of the malaria parasite Plasmodium falciparum is that the expression clusters of genes that code for enzymes engaged in the same cellular function is coordinated. Here the consistency of this perception is examined by analysing specific pathways that metabolically-linked. The pentose phosphate pathway (PPP) is a fundamental element of cell biochemistry since it is the major pathway for the recycling of NADP+ to NADPH and for the production of ribose-5-phosphate that is needed for the synthesis of nucleotides. The function of PPP depends on the synthesis of NADP+ and thiamine pyrophosphate, a co-enzyme of the PPP enzyme transketolase. In this essay, the transcription of gene coding for enzymes involved in the PPP, thiamine and NAD(P)+ syntheses are analysed. The genes coding for two essential enzymes in these pathways, transaldolase and NAD+ kinase could not be found in the genome of P. falciparum. It is found that the transcription of the genes of each pathway is not always coordinated and there is usually a gene whose transcription sets the latest time for the full deployment of the pathway's activity. The activity of PPP seems to involve only the oxidative arm of PPP that is geared for maximal NADP+ reduction and ribose-5-phosphate production during the early stages of parasite development. The synthesis of thiamine diphosphate is predicted to occur much later than the expression of transketolase. Later in the parasite cycle, the non-oxidative arm of PPP that can use fructose-6-phosphate and glyceraldehyde-3-phosphate supplied by glycolysis, becomes fully deployed allowing to maximize the production of ribose-5-phosphate. These discrepancies require direct biochemical investigations to test the activities of the various enzymes in the developing parasite. Notably, several transcripts of PPP enzyme-coding genes display biphasic pattern of transcription unlike most transcripts that peak only once during the parasite cycle. The physiological meaning of this pattern requires further investigation.
Highlights
The analysis of the transcriptome of Plasmodium falciparum has revealed that during the intraerythrocytic development of the parasite, genes coding for enzymes and proteins that are involved in complex cellular functions such as transcription, replication or energy metabolism, each involving many gene products, are transcribed in a coordinated fashion, supporting the notion that all components must be present at the right time to allow for optimal function [1,2,3]
NADPH can be produced during glucose-6-phosphate oxidation through the pentose-phosphate pathway (PPP; Figure 1)
Zerez et al [26] demonstrated 15-fold increase in the levels of NAD+ (NAD+ + NADH) in P. falciparum-infected erythrocytes, as well as 3-fold increase in nicotinate phosphoribosyltransferase (NAPRT) activity. These results indicate that the parasite is capable of NAD synthesis neither the activity of nicotinate-nucleotide adenylyltransferase or of NAD synthetase were increased in infected cells compared to uninfected erythrocytes
Summary
The analysis of the transcriptome of Plasmodium falciparum has revealed that during the intraerythrocytic development of the parasite, genes coding for enzymes and proteins that are involved in complex cellular functions such as transcription, replication or energy metabolism, each involving many gene products, are transcribed in a coordinated fashion, supporting the notion that all components must be present at the right time to allow for optimal function [1,2,3]. While this may be true in general, it has already been found that scrutinizing the details of specific metabolic functions reveal some significant (page number not for citation purposes). This pathway produces ribose-5-phosphate (R5P), the sugar component of nucleic acids
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