NUTRITIONAL-REQUIREMENTS OF PLASMODIUM-FALCIPARUM IN CULTURE .3. FURTHER OBSERVATIONS ON ESSENTIAL NUTRIENTS AND ANTIMETABOLITES
NUTRITIONAL-REQUIREMENTS OF PLASMODIUM-FALCIPARUM IN CULTURE .3. FURTHER OBSERVATIONS ON ESSENTIAL NUTRIENTS AND ANTIMETABOLITES
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DOI：
10.1111/j.1550-7408.1985.tb03087.x
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发表时间：
1985-01-01
期刊：
影响因子：
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通讯作者：
JENSEN, JB
中科院分区：
文献类型：
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作者：
GEARY, TG;DIVO, AA;JENSEN, JB
在用于培养恶性疟原虫的半限定基本培养基中，核糖、甘露糖、果糖、半乳糖和麦芽糖不能代替葡萄糖。次黄嘌呤是寄生虫的首选嘌呤来源，超过腺嘌呤、鸟嘌呤、肌苷、腺苷和鸟苷，尽管所有这些都同样支持。核苷摄取抑制剂杀死寄生虫的效力较低，但[3 H]腺苷的掺入比[3 H]次黄嘌呤更受抑制。谷氨酸不能被5-氧代脯氨酸替代，表明γ-脯氨酸不能被5-氧代脯氨酸替代。谷氨酰转移酶途径的氨基酸摄取可能没有发现在这种生物体。腺嘌呤、烟酰胺和乳清酸不能补充缺乏谷氨酰胺的培养基。吡哆醇拮抗剂异烟肼和4-deoxypyridoxine被逆转的氨基酸补充剂，这表明转氨酶可能是这些药物的目标。乳清酸，而不是谷胱甘肽或其氨基酸成分，部分逆转8-甲氨基-8-去甲基核黄素的影响。因此，黄素酶，二氢乳清酸脱氢酶，而不是谷胱甘肽还原酶，似乎是这种核黄素拮抗剂的目标。5种生物素拮抗剂无明显活性。胆碱拮抗剂2-（叔丁基氨基）乙醇和硫胺素摄取抑制剂具有非特异性抑制作用，这是不逆转各自的目标维生素。谷胱甘肽合成抑制剂丁硫氨酸亚砜亚胺和甲硫氨酸亚砜亚胺具有明显的氧依赖性毒性。六种磺胺类药物的效力和疗效存在明显差异。磺胺甲咪唑和磺胺嘧啶逆转差异对氨基苯甲酸，叶酸，亚叶酸。亚叶酸在逆转二氢叶酸还原酶抑制剂氨基蝶呤和乙胺嘧啶的毒性方面比叶酸更有效;对氨基苯甲酸没有影响。
In a semi-defined minimal medium for cultivation of Plasmodium falciparum ribose, mannose, fructose, galactose, and maltose could not replace glucose. Hypoxanthine was the preferred purine source for the parasite over adenine, guanine, inosine, adenosine and guanosine although all supported equally. Inhibitors of nucleoside uptake had low potency in killing the parasites but depressed incorporation of [3H]adenosine more than [3H]hypoxathine. Glutamate could not be replaced by 5-oxoproline, indicating that the .gamma.-glutamyl tranferase pathway for amino acid uptake is probably not found in this organism. Adenine, nicotinamide, and orotic acid could not supplement gutamine-deficient medium. The pyridoxine antagonists isoniazid and 4-deoxypyridoxine were reversed by amino acid supplementation, suggesting that transminases may be targets of these drugs. Orotic acid, but not glutathione or its amino acid components, partially reversed the effects of 8-methylamino-8-desmethyl riboflavin. Thus, the flavin enzyme, dihydroorotic acid dehydrogenase, but not glutathione reductase, appears to be a target of this riboflavin antagonist. Five biotin antagonists had no significant activity. The choline antagonist 2-(tert-butylamino)ethanol and thiamin uptake inhibitors had nonspecific inhibitory effects, which were not reversed by the respective target vitamin. Buthionine sulfoximine and methionine sulfoximine, inhibitors of glutathione synthesis, had significant oxygen-dependent toxicity. Six sulfonamides showed marked variation in potency and efficacy. Sulfathizole and sulfadoxine were reversed differentially by p-aminobenzoic acid, folic acid, and folinic acid. Folinic acid was more effective than folic acid at reversing the toxicity of the dihydrofolate reductase inhibitors aminopterin and pyrimethamine; p-aminobenzoic acid had no effect.