Aromatic amino acid catabolism in trypanosomatids.
Trypanosomatids cause important human diseases, like sleeping sickness, Chagas disease, and the leishmaniases. Unlike in the mammalian host, the metabolism of aromatic amino acids is a very simple pathway in these parasites. Trypanosoma brucei and Trypanosoma cruzi transaminate the three aromatic amino acids, the resulting 2-oxo acids being reduced to the corresponding lactate derivatives and excreted. In T. cruzi, two enzymes are involved in this process: a tyrosine aminotransferase (TAT), which despite a high sequence similarity with the mammalian enzyme, has a different substrate specificity; and an aromatic L-2-hydroxyacid dehydrogenase (AHADH), which belongs to the subfamily of the cytosolic malate dehydrogenases (MDHs), yet has no MDH activity. In T. cruzi AHADH the substitution of Ala102 for Arg enables AHADH to reduce oxaloacetate. In the members of the 2-hydroxyacid dehydrogenases family, the residue at this position is known to be responsible for substrate specificity. T. cruzi does not possess a cytosolic MDH but contains a mitochondrial and a glycosomal MDH; by contrast T. brucei and Leishmania spp. possess a cytosolic MDH in addition to glycosomal and mitochondrial isozymes. Although Leishmania mexicana also transaminates aromatic amino acids through a broad specificity aminotransferase, the latter presents low sequence similarity with TATs, and this parasite does not seem to have an enzyme equivalent to T. cruzi AHADH. Therefore, these closely related primitive eukaryotes have developed aromatic amino acid catabolism systems using different enzymes and probably for different metabolic purposes.
Nowicki
Cristina
C
IQUIFIB/Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, CP1113, Argentina. Electronic address: cnowicki@criba.edu.ar.
Cazzulo
Juan J
JJ
IIB-INTECH, Instituto de Investigaciones Biotecnológicas, Universidad Nacional de General San Martín-CONICET, Av. Gral. Paz y Albarellos, INTI, edificio 24, 1650 San Martín, Buenos Aires, Argentina.
D024322:Amino Acids, Aromatic / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D000637:Transaminases / Q000378:metabolism; D014351:Trypanosomatina / Q000378:metabolism*
D024322:Amino Acids, Aromatic; D000637:Transaminases