Figure 2: Metabolic parameters modulate reductive carboxylation.

(a) Lactate supplementation (25 mmol l⁻¹) in the media prohibits glucose conversion to lactate and thus forces an increased glucose contribution to the TCA cycle. Flux and metabolite state in standard growth condition (left), hypoxia or complex I/III inhibition (middle), and hypoxia or complex I/III inhibition with lactate (right). Thickness of the arrows and the size of the metabolites indicates the magnitude of alteration. AcCoA contribution to α-ketoglutarate (calculated from a U-¹³C glutamine tracer: M+3 from glutamine is highly correlated with M+2 from glucose in A549: R=0.998, P=0.0001) (b), α-ketoglutarate/citrate ratio (c) and reductive glutamine contribution to citrate (d) for different stress conditions with and without lactate supplementation. All error bars indicate the s.d. All P-values (Student’s t-test, two-tailed, unequal variance) and error bars are calculated from two independent replicates.