Figure 2. Citrate dilutes central carbon pathway labeling in hepatocellular carcinoma and neuronal cells in hypoxia.

(A) Atom transition map depicting catabolism of [U-¹³C₅]glutamine. Closed circles indicate ¹³C carbon, and open circles indicate ¹²C carbon.

(B) Mole percent enrichment of TCA intermediates from [U-¹³C₅]glutamine in Huh7 cells grown in hypoxia ± 500 μM citrate for 48 h, relative to (−) citrate (n = 3).

(C) Percent labeling of M3 aspartate from [U-¹³C₅]glutamine in HepG2 and Huh7 cells grown in hypoxia ± 500 μM citrate for 48 h (n = 3).

(D) Percentage of lipogenic acetyl-CoA contributed by [U-¹³C₅]glutamine in HepG2 and Huh7 cells grown in hypoxia ± 500 μM citrate for 48 h (n = 3).

(E) Mole percent enrichment of TCA intermediates from [U-¹³C₆]glucose in primary rat neuron cells grown in 3% oxygen ± 500 μM citrate for 48 h, relative to (−) citrate (n = 3).

(F) Percent of lipogenic acetyl-CoA contributed by [U-¹³C₆]glucose in primary rat neuron cells grown in 3% oxygen ± 500 μM citrate for 48 h (n = 3).

Asp, aspartate; Cit, citrate; α-KG, α-ketoglutarate; Fum, fumarate; Mal, malate. In (B), (C), and (E), data are plotted as mean ± SD. Statistical significance is relative to (−) citrate as determined by two-sided Student’s t test with *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. In (D) and (F), data are plotted as mean ± 95% confidence interval (CI). Asterisk (*) indicates statistical significance by non-overlapping CIs. Unless indicated, all data represent biological triplicates. Data shown are from one of at least two separate experiments. See also Figure S1.