Premium
The 2‐methylcitrate cycle is implicated in the detoxification of propionate in T oxoplasma gondii
Author(s) -
Limenitakis Julien,
Oppenheim Rebecca D.,
Creek Darren J.,
Foth Bernardo J.,
Barrett Michael P.,
SoldatiFavre Dominique
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12139
Subject(s) - biology , biochemistry , leucine , toxoplasma gondii , isoleucine , glyoxylate cycle , intracellular parasite , propionate , enzyme , amino acid , valine , mitochondrion , citric acid cycle , microbiology and biotechnology , intracellular , genetics , antibody
Summary T oxoplasma gondii belongs to the coccidian subgroup of the A picomplexa phylum. The C occidia are obligate intracellular pathogens that establish infection in their mammalian host via the enteric route. These parasites lack a mitochondrial pyruvate dehydrogenase complex but have preserved the degradation of branched‐chain amino acids ( BCAA ) as a possible pathway to generate acetyl‐ CoA . Importantly, degradation of leucine, isoleucine and valine could lead to concomitant accumulation of propionyl‐ CoA , a toxic metabolite that inhibits cell growth. Like fungi and bacteria, the C occidia possess the complete set of enzymes necessary to metabolize and detoxify propionate by oxidation to pyruvate via the 2‐methylcitrate cycle (2‐ MCC ). Phylogenetic analysis provides evidence that the 2‐ MCC was acquired via horizontal gene transfer. In T . gondii tachyzoites, this pathway is split between the cytosol and the mitochondrion. Although the rate‐limiting enzyme 2‐methylisocitrate lyase is dispensable for parasite survival, its substrates accumulate in parasites deficient in the enzyme and its absence confers increased sensitivity to propionic acid. BCAA is also dispensable in tachyzoites, leaving unresolved the source of mitochondrial acetyl‐ CoA .