Dieckmann A, Jung A
Mol Biochem Parasitol. 1986 May;19(2):143-7. doi: 10.1016/0166-6851(86)90119-2.
Three possible mechanisms of resistance to sulfadoxine were investigated in resistant Plasmodium falciparum: drug uptake, metabolism and alternate pathways. Uptake of [35S] sulfadoxine was markedly reduced in resistant plasmodia. By Thin Layer Radiochromatography it could be demonstrated that plasmodia do not metabolize sulfadoxine to pharmacologically inactive forms. Metabolism of sulfadoxine to the toxic analog of dihydropteroate is reduced in resistant plasmodia. Para-aminobenzoic acid (pABA) is not an essential nutrient for sulfonamide-resistant plasmodia. Instead, they seem to be able to synthesize pABA de novo. Four enzymes of the respective biosynthetic chain were demonstrated in isolated plasmodia: 3-deoxy-D-arabino-heptulosonate-7-phosphate synthetase (EC 4.2.1.15), shikimate dehydrogenase (EC 1.1.1.25), shikimate kinase (EC 2.7.1.71) and pABA synthetase. We conclude that these three effects account for the reduced sulfonamide stress observed in the resistant parasite.
药物摄取、代谢和替代途径。耐药疟原虫对[35S]磺胺多辛的摄取明显减少。通过薄层层析放射色谱法可以证明，疟原虫不会将磺胺多辛代谢为药理上无活性的形式。耐药疟原虫中磺胺多辛向二氢蝶酸毒性类似物的代谢减少。对氨基苯甲酸（pABA）不是耐磺胺疟原虫的必需营养素。相反，它们似乎能够从头合成pABA。在分离的疟原虫中证实了各自生物合成链的四种酶：3-脱氧-D-阿拉伯庚糖酸-7-磷酸合成酶（EC 4.2.1.15）、莽草酸脱氢酶（EC 1.1.1.25）、莽草酸激酶（EC 2.7.1.71）和pABA合成酶。我们得出结论，这三种效应导致了在耐药寄生虫中观察到的磺胺类药物应激减轻。
