Malate-Aspartate Shuttle Reversal Allows for Lactate Concentration Increases Upon Rapid Changes in 13C Pyruvate Concentration

Karlos X. Moreno¹, Scott Sabelhaus¹, Matthew E. Merritt¹, A Dean Sherry¹, Craig R. Malloy¹

The effect of [3-¹³C]pyruvate on [lactate] and [alanine] was studied in Langendorff-mode rat hearts. A 90 second perfusion with 2 mM [3-¹³C]pyruvate increased [lactate] and [alanine]. During the inhibition of aminotransferases by AOA, an increase in [alanine] was not observed, but, unexpectedly, [lactate] did not increase either. Lactate production was inhibited due to the lack of NADH replenishment from the malate-aspartate shuttle. These results support a reversal of the malate-aspartate shuttle to provide NADH for the production of lactate following a rapid increase in [pyruvate].