Fig. 1.

Metabolic pathways, including the urea cycle, TCA cycle, MA shuttle, and MC shuttle (a), and serum concentrations of amino acids related with the pathways (b). Asp that reacts with Cit to generate AS in the urea cycle is transported by AGC in exchange for Glu between the mitochondria and cytoplasm for the MA shuttle to maintain the NADH/NAD ratio in the cytoplasm. Asp is endogenously generated from Asn by asparaginase, and Glu is endogenously generated from Gln by glutaminase. In citrin deficiency, maintenance of the NADH/NAD ratio between the mitochondria and cytoplasm is compensated for by the MC shuttle, transporting MA by exchanging for Citr through CIC, and Citr is metabolized to Oxa in the cytoplasm. Data are presented as mean ± SD (μM). †P < 0.001 indicates a significant difference from the controls by the unpaired Student’s t-test. αKg α-ketoglutarate, AcCoA acetyl-CoA, AGC aspartate–glutamate carrier (citrin), Arg arginine, AS arginosuccinate, Asn asparagine, Asp asprartate, CIC citrate carrier, Cit citrulline, Citr citrate, Gln glutamine, Glu glutamate, MA shuttle malate–aspartate shuttle, Ma malate, MC shuttle malate–citrate shuttle, OGC oxoglutarate carrier, Orn ornithine, Oxa oxaloacetate