Van Hellemond J J, Opperdoes F R, Tielens A G
Laboratory of Veterinary Biochemistry and Institute of Biomembranes, Utrecht University, P. O. Box 80176, 3508 TD Utrecht, The Netherlands.
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3036-41. doi: 10.1073/pnas.95.6.3036.
Hydrogenosome-containing anaerobic protists, such as the trichomonads, produce large amounts of acetate by an acetate:succinate CoA transferase (ASCT)/succinyl CoA synthetase cycle. The notion that mitochondria and hydrogenosomes may have originated from the same alpha-proteobacterial endosymbiont has led us to look for the presence of a similar metabolic pathway in trypanosomatids because these are the earliest-branching mitochondriate eukaryotes and because they also are known to produce acetate. The mechanism of acetate production in these organisms, however, has remained unknown. Four different members of the trypanosomatid family: promastigotes of Leishmania mexicana mexicana, L. infantum and Phytomonas sp., and procyclics of Trypanosoma brucei were analyzed as well as the parasitic helminth Fasciola hepatica. They all use a mitochondrial ASCT for the production of acetate from acetyl CoA. The succinyl CoA that is produced during acetate formation by ASCT is recycled presumably to succinate by a mitochondrial succinyl CoA synthetase, concomitantly producing ATP from ADP. The ASCT of L. mexicana mexicana promastigotes was further characterized after partial purification of the enzyme. It has a high affinity for acetyl CoA (Km 0.26 mM) and a low affinity for succinate (Km 6.9 mM), which shows that significant acetate production can occur only when high mitochondrial succinate concentrations prevail. This study identifies a metabolic pathway common to mitochondria and hydrogenosomes, which strongly supports a common origin for these two organelles.
含氢化酶体的厌氧原生生物，如毛滴虫，通过乙酸：琥珀酸辅酶A转移酶（ASCT）/琥珀酰辅酶A合成酶循环产生大量乙酸。线粒体和氢化酶体可能起源于同一α-变形菌内共生体的观点，促使我们在锥虫中寻找类似的代谢途径，因为锥虫是最早分支的有线粒体的真核生物，而且它们也已知会产生乙酸。然而，这些生物体中乙酸的产生机制仍然未知。我们分析了锥虫科的四个不同成员：墨西哥利什曼原虫、婴儿利什曼原虫和植滴虫的前鞭毛体，以及布氏锥虫的前循环体，还有寄生蠕虫肝片吸虫。它们都利用线粒体ASCT从乙酰辅酶A产生乙酸。在通过ASCT形成乙酸的过程中产生的琥珀酰辅酶A，大概会通过线粒体琥珀酰辅酶A合成酶再循环为琥珀酸，同时由ADP产生ATP。对墨西哥利什曼原虫前鞭毛体的ASCT进行部分纯化后，对其进行了进一步表征。它对乙酰辅酶A具有高亲和力（Km 0.26 mM），对琥珀酸具有低亲和力（Km 6.9 mM），这表明只有当线粒体琥珀酸浓度较高时，才会发生大量乙酸的产生。这项研究确定了线粒体和氢化酶体共有的一种代谢途径，这有力地支持了这两个细胞器的共同起源。
