Fig. 1: Preferential reamination of α-ketoisovalerate (KIV) to valine in the isolated perfused heart.

a Simplified schematic figure diagraming the potential metabolic fates of [U-¹³C]KIV, as well as the effects of LY3351337 to inhibit BCAT activity, and BT2 to inhibit BDK. Label incorporation from first (red circles) and second (blue circles) passes through the TCA cycle are shown in dashed boxes. Measured metabolites in the TCA cycle are highlighted with a gray background and black dashed border. b The fractional percent labeling with ¹³C is shown for the indicated metabolites; (c) The absolute amounts of ¹³C-labeled valine, 3-HIB, citrate, and succinate are shown. Data in b–d are from hearts isolated from Wistar rats and perfused with [U-¹³C]KIV (100 μM) in the absence (Veh; n = 5; gray) or presence of the BDK inhibitor, BT2 (n = 4; red) or the BCAT inhibitor, LY3351337 (n = 6; blue). d Rate of reamination (nmol/min) of [U-¹³C]KIV to valine and rate of formation of ¹³C-labeled 3-HIB from [U-¹³C]KIV in isolated hearts following treatment with LY3351337 or BT2. Data represent mean ± SEM. Statistical differences indicated by Tukey’s HSD post-hoc test following one-way ANOVA: *P < 0.05, **P < 0.005, ***P < 0.0005.