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Sinefungin shares AdoMet-uptake system to enter Leishmania donovani promastigotes

M A Phelouzat1, M Basselin, F Lawrence

  • 1Institut de Chimie des Substances Naturelles, C.N.R.S., Gif-sur Yvette, France.

The Biochemical Journal
|January 1, 1995
PubMed

Insights

Sinefungin uptake in Leishmania donovani involves a carrier system. This system specifically transports sinefungin (SF) and S-adenosylmethionine (AdoMet), not common nucleosides.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Drug Transport Mechanisms

Background:

  • Leishmania donovani causes leishmaniasis.
  • Sinefungin (SF) is a potential anti-parasitic agent.
  • Understanding drug uptake is crucial for anti-parasitic drug development.

Purpose of the Study:

  • To investigate the carrier-mediated uptake of sinefungin (SF) in Leishmania donovani.
  • To determine if SF utilizes nucleoside or S-adenosylmethionine (AdoMet) carrier systems.

Main Methods:

  • Saturation kinetics and competition studies were employed.
  • Uptake of various molecules was compared in wild-type and SF-resistant cells.
  • Analysis of SF and AdoMet transport mechanisms.

Main Results:

  • SF uptake exhibited saturation kinetics and accumulation against a concentration gradient.
  • SF competitively inhibited AdoMet uptake but not purine or pyrimidine uptake.
  • SF-resistant cells showed similar nucleoside uptake but reduced SF and AdoMet uptake.

Conclusions:

  • Sinefungin uptake in Leishmania donovani is mediated by a specific carrier system.
  • This carrier system is shared with S-adenosylmethionine (AdoMet) but not with general nucleosides.
  • Findings provide insights into the transport of anti-parasitic agents.

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