Fig. 1.

HP [1-¹³C]pyruvate brain metabolism. Diagram of HP [1-¹³C]pyruvate metabolism in the brain, which is characterized by two primary pathways: enzymatic conversion of [1-¹³C]pyruvate to [1-¹³C]lactate via cytosolic lactate dehydrogenase (LDH); and successive conversion of [1-¹³C]pyruvate to ¹³CO₂ and [¹³C]bicarbonate via mitochondrial pyruvate dehydrogenase (PDH) and carbonic anhydrase (CA), respectively. The second-order kinetics of pyruvate-to-bicarbonate conversion are approximated by the rate-limiting step of PDH, given the rapid CO₂-bicarbonate exchange catalyzed by CA. HP [1-¹³C]pyruvate is also reversibly converted to [1-¹³C]alanine via alanine transaminase (ALT), but prior studies have shown that conversion to HP [1-¹³C]alanine occurs outside of the brain (4).