Burchmore, R.J.S. and Hart, D.T. (1995) Glucose transport in amastigotes and promastigotes of Leishmania mexicana mexicana. Molecular and Biochemical Parasitology, 74(1), pp. 77-86. (doi: 10.1016/0166-6851(95)02485-9) (PMID:8719247)
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Abstract
Promastigotes and amastigotes of Leishmania mexicana mexicana transported 2-deoxy-d-glucose (2-DOG) by a saturable process with a Km of 24 ± 3 μM and Vmax of 2.21 nmol min−1 (mg protein)−1 for the promastigote and a Km of 29 ± 8 μM and Vmax of 0.13 nmol min−1 (mg protein)−1 for the amastigote stage. Amastigotes incorporated 2-DOG maximally at pH 5.0, while for promastigotes the optimum was at pH 7.0. Mid-log phase promastigotes were found to accumulate 2-DOG via a stereospecific carrier-mediated process which was competitively inhibited by d-glucose and d-mannose but not l-glucose. Transport was dependent upon temperature, with a Q10 in promastigotes of 1.83 and an optimum rate at 35°C (±4°C) with an activation energy of 50.12 kJ mol−1. Stationary phase promastigotes accumulated 2-DOG at approximately twice the rate of mid-log phase promastigotes. Cytochalasin B, forskolin and phloretin were all found to inhibit human erythrocyte 2-DOG uptake but only cytochalasin B was found significantly to inhibit promastigote 2-DOG uptake. Interestingly, leishmanial 2-DOG uptake was inhibited by a series of membrane potential antagonists including the ionophore monensin, the H+ATPase inhibitor N,N′-dicyclohexylcarbodiimide (DCCD) and uncoupling agent carbonylcyanide-4-(triflouromethoxy) phenylhydrazone (FCCP), as well as, the tricyclic drugs chlomipramine and imipramine, but was insensitive to the Na+/K+ ATPase inhibitor ouabain and the antitrypanosomal drugs Pentostam and Suramin. We therefore conclude that there are significant structural and mechanistic differences between the d-glucose uptake systems of Leishmania and the mammalian host to merit the inclusion of glucose transporters as putative targets for rational drug design.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Burchmore, Dr Richard |
Authors: | Burchmore, R.J.S., and Hart, D.T. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Molecular and Biochemical Parasitology |
Publisher: | Elsevier BV |
ISSN: | 0166-6851 |
ISSN (Online): | 1872-9428 |
Published Online: | 06 April 2000 |
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