2-Methylcitric acid

2-Methylcitric acid (Methylcitric acid) is an endogenous metabolite in the 2-methylcitric acid cycle. 2-Methylcitric acid accumulates in methylmalonic and propionic acidemias and acts as a marker metabolite. 2-Methylcitric acid markedly inhibits ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate^[1]. In Vitro: 2-Methylcitric acid (Methylcitric acid) impairs glutamate metabolism and induces permeability transition in brain mitochondria. 2-Methylcitric acid inhibits glutamate dehydrogenase (GDH) activity at concentrations as low as 0.5 mM^[1].
2-Methylcitric acid (1-3 mM; 150 seconds) provokes a significant decrease in mitochondrial membrane potential and induced swelling in Ca²⁺-loaded mitochondria supported by different substrates^[1].
2-Methylcitric acid behaves as a potent inhibitor of glutamate oxidation by inhibiting glutamate dehydrogenase activity and as a permeability transition inducer, disturbing mitochondrial energy homeostasis. 2-Methylcitric acid does not significantly impair mitochondrial glutamate transport. 2-Methylcitric acid does not significantly impair glutamate mitochondrial transport in liver mitochondria^[1].