Functional and structural resilience of the active site loop in the evolution of <i>Plasmodium</i> lactate dehydrogenase

Wirth, Jacob D.; Boucher, Jeffrey I.; Jacobowitz, Joseph; Classen, Scott; Theobald, Douglas L.

doi:10.1101/386029

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…Within infected erythrocytes, most of the glucose (60-70%) is incompletely oxidized to lactate and excreted [29]. High lactate dehydrogenase activity, which produces lactate from pyruvate, generates oxidized nicotinamide adenine dinucleotide (NAD + ) from reduced nicotinamide adenine dinucleotide (NADH) [37]. This process can generate nicotinic acid mononucleotide as a byproduct, which increased 33-fold in abundance (Table 2).…”

Section: Metabolite Changes Characterizing Uninfected and Infected Ermentioning

confidence: 99%

Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite

Tewari

Swift

Reifman

et al. 2020

Malar J

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Background: Human blood cells (erythrocytes) serve as hosts for the malaria parasite Plasmodium falciparum during its 48-h intraerythrocytic developmental cycle (IDC). Established in vitro protocols allow for the study of host-parasite interactions during this phase and, in particular, high-resolution metabolomics can provide a window into host-parasite interactions that support parasite development. Methods: Uninfected and parasite-infected erythrocyte cultures were maintained at 2% haematocrit for the duration of the IDC, while parasitaemia was maintained at 7% in the infected cultures. The parasite-infected cultures were synchronized to obtain stage-dependent information of parasite development during the IDC. Samples were collected in quadruplicate at six time points from the uninfected and parasite-infected cultures and global metabolomics was used to analyse cell fractions of these cultures. Results: In uninfected and parasite-infected cultures during the IDC, 501 intracellular metabolites, including 223 lipid metabolites, were successfully quantified. Of these, 19 distinct metabolites were present only in the parasite-infected culture, 10 of which increased to twofold in abundance during the IDC. This work quantified approximately five times the metabolites measured in previous studies of similar research scope, which allowed for more detailed analyses. Enrichment in lipid metabolism pathways exhibited a time-dependent association with different classes of lipids during the IDC. Specifically, enrichment occurred in sphingolipids at the earlier stages, and subsequently in lysophospholipid and phospholipid metabolites at the intermediate and end stages of the IDC, respectively. In addition, there was an accumulation of 18-, 20-, and 22-carbon polyunsaturated fatty acids, which produce eicosanoids and promote gametocytogenesis in infected erythrocyte cultures. Conclusions: The current study revealed a number of heretofore unidentified metabolic components of the hostparasite system, which the parasite may exploit in a time-dependent manner to grow over the course of its development in the blood stage. Notably, the analyses identified components, such as precursors of immunomodulatory molecules, stage-dependent lipid dynamics, and metabolites, unique to parasite-infected cultures. These conclusions are reinforced by the metabolic alterations that were characterized during the IDC, which were in close agreement with those known from previous studies of blood-stage infection.

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Section: Metabolite Changes Characterizing Uninfected and Infected Ermentioning

confidence: 99%

Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite

Tewari

Swift

Reifman

et al. 2020

Malar J

View full text Add to dashboard Cite

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Rational engineering of the Plasmodium falciparum l-lactate dehydrogenase loop involved in catalytic proton transfer to improve chiral 2-hydroxybutyric acid production

Tian

Zhou

et al. 2021

International Journal of Biological Macromolecules

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Functional and structural resilience of the active site loop in the evolution of Plasmodium lactate dehydrogenase

Cited by 2 publications

References 32 publications

Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite

Metabolic alterations in the erythrocyte during blood-stage development of the malaria parasite

Rational engineering of the Plasmodium falciparum l-lactate dehydrogenase loop involved in catalytic proton transfer to improve chiral 2-hydroxybutyric acid production

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