Figure 3. Exogenous citrate is metabolized for TCA anaplerosis and fatty acid synthesis.

(A) Mole percent enrichment of TCA intermediates from [2,4-¹³C₂]citrate in Huh7 (left) and HepG2 (right) cells grown in normoxia or hypoxia for 48 h (n = 3).

(B) Mole percent enrichment of TCA intermediates from [2,4-¹³C₂]citrate in primary rat neuron cells grown in normoxia or 3% oxygen for 48 h (n = 3).

(C) Mole percent enrichment of fatty acids from [2,4-¹³C₂]citrate in Huh7 (left) and HepG2 (right) cells grown in normoxia or hypoxia for 48 h (n = 3).

(D) Mole percent enrichment of fatty acids from [2,4-¹³C₂]citrate in primary rat neuron cells grown in normoxia or 3% oxygen for 48 h (n = 3).

(E) Percent of lipogenic acetyl-CoA contributed by [U-¹³C₆]glucose, [U-¹³C₅]glutamine, and [2,4-¹³C₂]citrate, in the presence or absence of 500 μM unlabeled citrate in Huh7 (left) and HepG2 (right) cells grown in hypoxia for 48 h (n = 3).

Cit, citrate; α-KG, α-ketoglutarate; Suc, succinate; Fum, fumarate; Mal, malate; Asp, aspartate; Glu, glutamate; Gln, glutamine; Glc, glucose. In (A)–(D), data are plotted as means ± SD. Statistical significance is relative to normoxia as determined by two-sided Student’s t test with *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. Unless indicated, all data represent biological triplicates. In (E), data are plotted as mean ± 95% CI. Asterisk (*) indicates statistical significance by non-overlapping CIs. Data shown are from one of at least two separate experiments. See also Figure S2.