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1.
Biosci Rep ; 34(6): e00150, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25405893

RESUMO

Although efforts to understand the basis for inter-strain phenotypic variation in the most virulent malaria species, Plasmodium falciparum, have benefited from advances in genomic technologies, there have to date been few metabolomic studies of this parasite. Using 1H-NMR spectroscopy, we have compared the metabolite profiles of red blood cells infected with different P. falciparum strains. These included both chloroquine-sensitive and chloroquine-resistant strains, as well as transfectant lines engineered to express different isoforms of the chloroquine-resistance-conferring pfcrt (P. falciparum chloroquine resistance transporter). Our analyses revealed strain-specific differences in a range of metabolites. There was marked variation in the levels of the membrane precursors choline and phosphocholine, with some strains having >30-fold higher choline levels and >5-fold higher phosphocholine levels than others. Chloroquine-resistant strains showed elevated levels of a number of amino acids relative to chloroquine-sensitive strains, including an approximately 2-fold increase in aspartate levels. The elevation in amino acid levels was attributable to mutations in pfcrt. Pfcrt-linked differences in amino acid abundance were confirmed using alternate extraction and detection (HPLC) methods. Mutations acquired to withstand chloroquine exposure therefore give rise to significant biochemical alterations in the parasite.


Assuntos
Metaboloma , Metabolômica/métodos , Plasmodium falciparum/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/métodos , Animais , Antimaláricos/farmacologia , Cloroquina/farmacologia , Cromatografia Líquida de Alta Pressão , Resistência a Medicamentos/efeitos dos fármacos , Resistência a Medicamentos/genética , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Feminino , Interações Hospedeiro-Parasita , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Mutação , Oócitos/metabolismo , Plasmodium falciparum/genética , Plasmodium falciparum/fisiologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Especificidade da Espécie , Trofozoítos/metabolismo , Trofozoítos/fisiologia , Xenopus laevis
2.
NMR Biomed ; 22(3): 292-302, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19021153

RESUMO

NMR spectroscopy was used to identify and quantify compounds in extracts prepared from mature trophozoite-stage Plasmodium falciparum parasites isolated by saponin-permeabilisation of the host erythrocyte. One-dimensional (1)H NMR spectroscopy and four two-dimensional NMR techniques were used to identify more than 50 metabolites. The intracellular concentrations of over 40 metabolites were estimated from the (1)H NMR spectra of extracts prepared by four extraction methods: perchloric acid, methanol/water, methanol/chloroform/water, and methanol alone. The metabolites quantified included: the majority of the biological alpha-amino acids; 4-aminobutyric acid; mono-, di- and tri-carboxylic acids; nucleotides; polyamines; myo-inositol; and phosphocholine and phosphoethanolamine. The parasites also contained a significant concentration (up to 12 mM) of the exogenous buffering agent, HEPES. Although the metabolite profiles obtained with each extraction method were broadly similar, perchloric acid was found to have significant advantages over the other extraction media.


Assuntos
Eritrócitos/parasitologia , Malária Falciparum/parasitologia , Metabolômica , Parasitos/metabolismo , Plasmodium falciparum/metabolismo , Animais , Extratos Celulares , Centrifugação , Espaço Intracelular , Análise dos Mínimos Quadrados , Espectroscopia de Ressonância Magnética , Análise Multivariada , Parasitos/isolamento & purificação , Plasmodium falciparum/isolamento & purificação , Trofozoítos/metabolismo
3.
J Biol Chem ; 282(35): 25395-405, 2007 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-17581817

RESUMO

To survive, the human malaria parasite Plasmodium falciparum must acquire pantothenate (vitamin B5) from the external medium. Pantothenol (provitamin B5) inhibits parasite growth by competing with pantothenate for pantothenate kinase, the first enzyme in the coenzyme A biosynthesis pathway. In this study we investigated pantothenol uptake by P. falciparum and in doing so gained insights into the regulation of the parasite's coenzyme A biosynthesis pathway. Pantothenol was shown to enter P. falciparum-infected erythrocytes via two routes, the furosemide-inhibited "new permeation pathways" induced by the parasite in the infected erythrocyte membrane (the sole access route for pantothenate) and a second, furosemide-insensitive pathway. Having entered the erythrocyte, pantothenol is taken up by the intracellular parasite via a mechanism showing functional characteristics distinct from those of the parasite's pantothenate uptake mechanism. On reaching the parasite cytosol, pantothenol is phosphorylated and thereby trapped by pantothenate kinase, shown here to be under feedback inhibition control by coenzyme A. Furosemide reduced this inherent feedback inhibition by competing with coenzyme A for binding to pantothenate kinase, thereby increasing pantothenol uptake.


Assuntos
Coenzima A/metabolismo , Citoplasma/enzimologia , Ácido Pantotênico/análogos & derivados , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Plasmodium falciparum/enzimologia , Proteínas de Protozoários/metabolismo , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/parasitologia , Furosemida/farmacologia , Humanos , Ácido Pantotênico/metabolismo , Ácido Pantotênico/farmacologia , Ligação Proteica/efeitos dos fármacos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacologia , Complexo Vitamínico B/metabolismo , Complexo Vitamínico B/farmacologia
5.
J Asian Nat Prod Res ; 6(3): 205-9, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15224418

RESUMO

Two new tirucallane-type triterpenoid saponins, sapimukoside C (1) and sapimukoside D (2), have been isolated from the roots of Sapindus mukorossi Gaetn. Their structures have been determined, on the basis of spectral and chemical analysis, as 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L- arabinopyranosyl-(1-->3)]-beta-D-glucopyranosyl (21,23R)-epoxyl tirucalla-7,24-diene-(21S)-ethoxyl-3 beta-ol (1) and 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-arabinopyranosyl-(1-->3)]- beta-D-glucopyranosyl (21,23R)-epoxyl tirucall-7,24-diene-(21S)-methoxyl-3 beta-ol (2).


Assuntos
Fitoterapia , Extratos Vegetais/química , Sapindus , Saponinas/química , Triterpenos/química , Humanos , Espectroscopia de Ressonância Magnética , Raízes de Plantas
6.
J Asian Nat Prod Res ; 5(2): 75-82, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12765190

RESUMO

Four new oleanane type saponins, monepalosides G-J (1-4), were isolated from the water-soluble part of the whole plant of Morina nepalensis var. alba Hand-Mazz. On the basis of chemical and spectroscopic evidence, their structures were determined as 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-alpha-L-arabinopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside (monepaloside G, 1), 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-beta-D-xylopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside (monepaloside H, 2), 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-[beta-D-glucopyranosyl-(1 --> 2)]-alpha-L-arabinopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside (monepaloside I, 3), 3-O-beta-D-glucopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 3)]-alpha-L-arabinopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside (monepaloside J, 4), respectively. Two-dimensional NMR spectra, including H-H COSY, HMQC, 2D HMQC-TOCSY, HMBC and ROESY were utilized in the structure elucidation and complete assignments of 1H and 13C NMR spectra.


Assuntos
Magnoliopsida/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , China , Medicamentos de Ervas Chinesas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais , Saponinas/química , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Triterpenos/química
7.
J Nat Prod ; 65(5): 750-2, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12027759

RESUMO

Five novel alkaloids, brachystemidines A-E (1-5), were isolated from the roots of Brachystemma calycinum. Their structures were established by spectral data, especially by 1D and 2D NMR techniques. The crystal structure of brachystemidine D was determined via X-ray diffraction analysis.


Assuntos
Alcaloides/isolamento & purificação , Caryophyllaceae/química , Medicamentos de Ervas Chinesas/química , Plantas Medicinais/química , Alcaloides/química , Cristalografia por Raios X , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química
8.
Fitoterapia ; 73(1): 95-6, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11864769

RESUMO

A novel acylated flavonol glycoside, quercetin 3-O-[2' "-O-(E)-caffeoyl]-alpha-L-arabinopyranosyl-(1-->6)-beta-D-galactopyranoside (1), was isolated from whole plant of Morina nepalensis var. alba. Its structure was determined on the basis of chemical and spectroscopic methods.


Assuntos
Flavonoides/química , Glicosídeos/química , Magnoliopsida , Fitoterapia , Extratos Vegetais/química , Flavonoides/isolamento & purificação , Flavonóis , Glicosídeos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Extratos Vegetais/isolamento & purificação
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