Mechanism of acetate production
It has long remained an unsolved question by what mechanism the procyclic stages of T. brucei, as well as the other insect stages of trypanosomatids, produce their acetate. Since procyclics have a functional pyruvate dehydrogenase complex (Jackman, S. and Opperdoes, unpublished) and citric-acid cycle in the mitochondrion, they must be capable of converting pyruvate to acetylCoA. Due to the limited capacity of the cycle not all acetylCoA can be oxidised and a considerable amount is excreted in the form of acetate. Recently it has been shown that both in Leishmania promastigotes and in T. brucei procyclics, acetate is produced from acetyl-CoA with the synthesis of one molecule of ATP by a cycle that comprises a novel mitochondrial acetate:succinate CoA-transferase (Van Hellemond et al., 1998) and the ATP-dependent citric-acid-cycle enzyme succinyl-CoA synthase (Jenkins et al., 1988). The acetate:succinate CoA-transferase of L. mexicana mexicana promastigotes was shown to have a high affinity for acetyl-CoA (Km 0.1 mM), while it has a low affinity for succinate (Km 3.8 mM). This suggests that acetate production only occurs when mitochondrial succinate concentrations are high and thus the intra-mitochondrial succinate concentration would be a key-factor in switching mitochondrial metabolism from citric-acid cycle activity to the production of acetate. Interestingly, a similar pathway for the production of acetate has since long been known to be associated with hydrogenosomes, the hydrogen-producing organelles of the facultative anaerobe Trichomonas sp. (Lindmark, 1976). Now that it has become likely that mitochondria and hydrogenosomes are the descendants of the same alpha-proteobacterial endosymbiont (Müller, 1997), the identification of the acetate:succinate CoA transferase/succinyl-CoA synthase cycle in the mitochondria of trypanosomatids is the first metabolic pathway common to both types of organelle.