Figure 1.

Schematic showing how the metabolites derived from (A) [U-¹³C]glutamine can be traced through the oxidative and reductive glutamine pathways and (B) [1-¹³C]glutamine can be traced through the reductive glutamine pathway. In the Gln-Glu-a-KG pathway, white circles represent ¹²Carbon, while solid black circles represent ¹³Carbon. Blue circles represent ¹³C in the oxidative glutamine metabolism pathway of the TCA cycle and the citrate shuttle, while red circles represent ¹³C in the reductive carboxylation pathways in either mitochondria or cytoplasm. The green arrow indicates the shift toward lipid metabolism. For [U-¹³C]glutamine in (A), abbreviations are as follows: for the Gln-Glu-α-KG pathway: Gln, M5 glutamine; Glu, M5 glutamate; α-KG, M5 α-ketoglutarate. For oxidative glutamine metabolism: Suc, M4 succinate; Fum, M4 fumarate; Mal, M4 malate; Oac, M4 oxaloacetate; Cit, M4 citrate; Lac, M3 lactate. For reductive carboxylation: Ict, M5 isocitrate; Cit, M5 citrate; Oac, M3 oxaloacetate; Asp, M3 aspartate; Fum, M3 fumarate; Mal, M3 malate. Similar abbreviations apply for [1-¹³C]glutamine (M1 glutamine) in (B).