Intraerythrocytic stages of <i>Plasmodium falciparum</i>
 biosynthesize vitamin E

Sussmann, Rodrigo Antonio Ceschini; Angeli, Cláudia Blanes; Peres, Valnice J.; Kimura, Emı́lia A.; Katzin, Alejandro M.

doi:10.1016/j.febslet.2011.11.005

Cited by 44 publications

(68 citation statements)

References 37 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The group of compounds collectively known as vitamin E (tocopherols and tocotrienols) function as antioxidants and membrane stabilizers (75)(76)(77) (78).…”

Section: Sesquiterpenes and Diterpenesmentioning

confidence: 99%

Isoprenoid Biosynthesis in Plasmodium falciparum

2014

View full text Add to dashboard Cite

bMalaria kills nearly 1 million people each year, and the protozoan parasite Plasmodium falciparum has become increasingly resistant to current therapies. Isoprenoid synthesis via the methylerythritol phosphate (MEP) pathway represents an attractive target for the development of new antimalarials. The phosphonic acid antibiotic fosmidomycin is a specific inhibitor of isoprenoid synthesis and has been a helpful tool to outline the essential functions of isoprenoid biosynthesis in P. falciparum. Isoprenoids are a large, diverse class of hydrocarbons that function in a variety of essential cellular processes in eukaryotes. In P. falciparum, isoprenoids are used for tRNA isopentenylation and protein prenylation, as well as the synthesis of vitamin E, carotenoids, ubiquinone, and dolichols. Recently, isoprenoid synthesis in P. falciparum has been shown to be regulated by a sugar phosphatase. We outline what is known about isoprenoid function and the regulation of isoprenoid synthesis in P. falciparum, in order to identify valuable directions for future research.

show abstract

“…The group of compounds collectively known as vitamin E (tocopherols and tocotrienols) function as antioxidants and membrane stabilizers (75)(76)(77) (78).…”

Section: Sesquiterpenes and Diterpenesmentioning

confidence: 99%

Isoprenoid Biosynthesis in Plasmodium falciparum

2014

View full text Add to dashboard Cite

show abstract

“…Growth inhibition by usnic acid, which inhibits vitamin E synthesis, was accompanied by a decline in vitamin E concentrations, but only partially rescued by addition of alpha-tocopherol. Alpha tocopherol synthesis increased by 40% under high (20%) oxygen, suggesting a role for vitamin E in protection from oxidative stress [98]. …”

Section: Introductionmentioning

confidence: 99%

Isoprenoid Metabolism in Apicomplexan Parasites

Imlay

Odom

2014

Curr Clin Micro Rpt

View full text Add to dashboard Cite

Apicomplexan parasites include some of the most prevalent and deadly human pathogens. Novel antiparasitic drugs are urgently needed. Synthesis and metabolism of isoprenoids may present multiple targets for therapeutic intervention. The apicoplast-localized methylerythritol phosphate (MEP) pathway for isoprenoid precursor biosynthesis is distinct from the mevalonate (MVA) pathway used by the mammalian host, and this pathway is apparently essential in most Apicomplexa. In this review, we discuss the current field of research on production and metabolic fates of isoprenoids in apicomplexan parasites, including the acquisition of host isoprenoid precursors and downstream products. We describe recent work identifying the first MEP pathway regulator in apicomplexan parasites, and introduce several promising areas for ongoing research into this well-validated antiparasitic target.

show abstract

“…Our results also indicate that this biosynthesis can be strongly inhibited by the HPPD irreversible enzyme‐binding inhibitor usnic acid and moderately by HPPD inhibitor nitisinone , possibly due to its reversible enzyme‐binding in most studied organisms . The 4‐hydroxyphenylpyruvate dioxygenase catalyses the conversion of p ‐hydroxyphenylpyruvic acid to homogentisic acid , a direct precursor of vitamin E and plastoquinone in most photosynthetic organisms except in cyanobacteria, where plastoquinone is thought to be biosynthesized by an alternative pathway .…”

Section: Discussionmentioning

confidence: 65%

Tocopherol biosynthesis in Leishmania (L.) amazonensis promastigotes

et al. 2019

Self Cite

View full text Add to dashboard Cite

Leishmaniasis is a neglected disease caused by a trypanosomatid protozoan of the genus Leishmania. Most drugs used to treat leishmaniasis are highly toxic, and the emergence of drug‐resistant strains has been observed. Therefore, new therapeutic targets against leishmaniasis are required. Several isoprenoid compounds, including dolichols or ubiquinones, have been shown to be important for cell viability and proliferation in various trypanosomatid species. Here, we detected the biosynthesis of tocopherol in Leishmania (L.) amazonensis promastigotes in vitro through metabolic labelling with [1‐(n)‐3H]‐phytol. Subsequently, we confirmed the presence of vitamin E in the parasite by gas chromatography–mass spectrometry. Treatment with usnic acid or nitisinone, inhibitors of precursors of vitamin E synthesis, inhibited growth of the parasite in a concentration‐dependent manner. This study provides the first evidence of tocopherol biosynthesis in a trypanosomatid and suggests that inhibitors of the enzyme 4‐hydroxyphenylpyruvate dioxygenase may be suitable for use as antileishmanial compounds. Database The amino acid sequence of a conserved hypothetical protein [Leishmania mexicana MHOM/GT/2001/U1103] has been deposited in GenBank ()

show abstract

Intraerythrocytic stages of Plasmodium falciparum biosynthesize vitamin E

Cited by 44 publications

References 37 publications

Isoprenoid Biosynthesis in Plasmodium falciparum

Isoprenoid Biosynthesis in Plasmodium falciparum

Isoprenoid Metabolism in Apicomplexan Parasites

Tocopherol biosynthesis in Leishmania (L.) amazonensis promastigotes

Contact Info

Product

Resources

About