Evidence map›Paper›PMID 38918706›Full record

ArticleBMC infectious diseases2024

Metabolism of FAD, FMN and riboflavin (vitamin B2) in the human parasitic blood fluke Schistosoma mansoni.

Akram A Da'dara, Catherine S Nation, Patrick J Skelly

Abstract read
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Article in BMC infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Akram A Da'daraMolecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA.
Catherine S NationMolecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA.
Patrick J SkellyMolecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA. Patrick.Skelly@Tufts.edu.

Funding

Gene silencing in schistosomes using RNAiR01AI056273 · NIAID · TUFTS UNIVERSITY BOSTON · PI Patrick J Skelly · 2004 to 2026
$7.2M
Functional Characterization of the Schistosome TegumentR56AI056273 · NIAID · TUFTS UNIVERSITY BOSTON · PI SKELLY, PATRICK J · 2021 to 2021
$413k
National Institute of Allergy and Infectious Diseases AI056273NIAID NIH HHS R01 AI056273NIAID NIH HHS R56 AI056273
6 · The paper itself

Abstract

backgroundSchistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes.

methodsHere, using a combination of metabolomics, enzyme kinetics and in silico molecular analysis, we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni (Sm).

resultsWe show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while levels of FMN increase. We show that live schistosomes cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface nucleotide pyrophosphatase/phosphodiesterase ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM and Kcat/Km of 324,734 ± 36,347 M

conclusionsThe sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by the recently described schistosome riboflavin transporter SmaRT. Finally, we identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes.

Indexed as

Flavin-Adenine DinucleotideFlavin MononucleotideRiboflavinSchistosoma mansoniAnimalsHumansMiceSchistosomiasis mansoniFlavin-Adenine DinucleotideFlavin MononucleotideRiboflavinEctoenzymeHost-parasite interactionSchistosome

Identifiers

PMID38918706
PMCPMC11202380

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.