Krungkrai J, Webster H K, Yuthavong Y
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
Mol Biochem Parasitol. 1989 Jan 1;32(1):25-37. doi: 10.1016/0166-6851(89)90126-6.
Plasmodium falciparum was shown to synthesize pteroylpolyglutamate de novo from guanosine 5'-triphosphate (GTP), p-aminobenzoate (PABA), and L-glutamate (L-Glu). The parasite also had the capacity to synthesize pteroylpolyglutamate from both intact and degradation moieties (p-aminobenzoylglutamate and pterin-aldehyde) of exogenous folate added into the growth medium. The major product was identified as 5-methyl-tetrahydroteroylpentaglutamate following exposure to pteroylpolyglutamate hydrolase and oxidative degradation of the C9-N10 bond in the molecule and identification of products by reversed-phase high performance liquid chromatography. Inhibition of pteroylpentaglutamate synthesis from the radiolabelled metabolic precursors (GTP, PABA, L-Glu) and folate by the antifolate antimalarials, pyrimethamine and sulfadoxine at therapeutic concentrations, may suggest the existence of a unique biosynthetic pathway in the malaria parasite.
恶性疟原虫被证明能从鸟苷 5'-三磷酸（GTP）、对氨基苯甲酸（PABA）和 L-谷氨酸（L-Glu）从头合成蝶酰多谷氨酸。该寄生虫也有能力从添加到生长培养基中的外源性叶酸的完整部分和降解部分（对氨基苯甲酰谷氨酸和蝶呤醛）合成蝶酰多谷氨酸。在将产物暴露于蝶酰多谷氨酸水解酶并氧化降解分子中的 C9-N10 键，然后通过反相高效液相色谱法鉴定产物后，主要产物被鉴定为 5-甲基-四氢蝶酰五谷氨酸。治疗浓度的抗叶酸抗疟药乙胺嘧啶和磺胺多辛对来自放射性标记的代谢前体（GTP、PABA、L-Glu）和叶酸的蝶酰五谷氨酸合成的抑制，可能表明疟原虫中存在独特的生物合成途径。
