Figure 1. Metabolism of co-infused [1,6-¹³C]glucose and [1,2-¹³C]acetate.

(A) Low power hematoxylin & eosin (H&E) of a GBM HOT mouse brain at the time of co-infusion. (a) A large tumor (T) mass is seen in the right hemisphere. The left hemisphere is designated non-tumor (NT) brain. Scale bar 0.3 cm. High power images from (b) tumor (T) and (c) NT brain (scale bars 10 µm), and (d) tumor infiltrating brain at the edge of the mass (scale bar 20 µm). (B) Schema showing the fate of individual carbons from infused [1,6-¹³C]glucose (blue filled circles-¹³C) and [1,2-¹³C]acetate (red filled circles-¹³C) through the first turn of the CAC and labeling in α-KG, GLU and GLN after multiple turns. Open circles ¹²C. Numbers refer to carbon positions. Abbreviations: LAC, lactate; Ac-CoA, acetyl CoA; CIT, citrate; α-KG, α- ketoglutarate; GLU, glutamate; GLN, glutamine; OAA, oxaloacetate; PDH, pyruvate dehydrogenase; LDH, lactate dehydrogenase; PYR, pyruvate. (C) ¹³C-NMR spectrum from NT brain after co-infusion. Insets are GLU4 and GLN4. Singlet (S) and doublet 3,4 (D34) in blue are generated from ¹³C-glucose metabolism and doublets 4,5 (D45) in red are generated from ¹³C-acetate metabolism. The color scheme is the same in all figures. Chemical shift assignments: 1, Alanine C3; 2, Lactate C3; 3, N-acetylaspartate C6; 4, GABA C3; 5, Glutamine C3; 6, Glutamate C3; 7, Glutamine C4; 8, Glutamate C4; 9, GABA C2; 10, Aspartate C3; 11, GABA C4; 12, Taurine (?); 13, Aspartate C2; 14, Glutamine C2; 15, Glutamate C2.