Sagar R, Salotra P, Bhatnagar R, Datta K
Biochemistry Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India.
Microbiol Res. 1995 Nov;150(4):419-23. doi: 10.1016/S0944-5013(11)80024-8.
Leishmania protozoans are the causative agents of leishmaniasis, a major parasitic disease in humans. The parasites manifest a nutritional requirement for heme compounds since they are deficient in heme biosynthesis. In this study we have demonstrated for the first time the presence of the enzyme L-alanine: 4,5-dioxovalerate transaminase in Leishmania donovani. This enzyme catalyzes the synthesis of 5-aminolevulinic acid (ALA), the first committed step in heme synthesis. Thus the defect in heme biosynthesis pathway in Leishmania must lie at some enzymatic level subsequent to synthesis of ALA. The enzyme was found to be present in both virulent and avirulent strains of L. donovani. The virulent promastigotes showed a 41% higher specific activity as compared to the avirulent strain. The enzyme activity was found to be inhibited in the presence of heme and methylglyoxal. Immunoblot analysis revealed that L-alanine: 4,5-dioxovalerate transaminase in L. donovani was immunologically different from that in mammals.
利什曼原虫是利什曼病的病原体,利什曼病是人类主要的寄生虫病。由于这些寄生虫在血红素生物合成方面存在缺陷,它们对血红素化合物有营养需求。在本研究中,我们首次证明了杜氏利什曼原虫中存在L-丙氨酸:4,5-二氧戊酸转氨酶。该酶催化5-氨基酮戊酸(ALA)的合成,这是血红素合成的第一个关键步骤。因此,利什曼原虫血红素生物合成途径的缺陷必定存在于ALA合成之后的某个酶促水平。发现该酶存在于杜氏利什曼原虫的强毒株和无毒株中。与无毒株相比,强毒前鞭毛体的比活性高41%。发现该酶活性在血红素和甲基乙二醛存在时受到抑制。免疫印迹分析表明,杜氏利什曼原虫中的L-丙氨酸:4,5-二氧戊酸转氨酶在免疫上与哺乳动物中的不同。