FIGURE 7.

Role of CoA in the formation of TCA cycle‐related metabolites. There are two key, irreversible steps (green arrows) that depend on CoASH in the TCA cycle: pyruvate dehydrogenase and α‐ketoglutarate dehydrogenase. The block at propionyl‐CoA carboxylase (yellow) leads to the accumulation of C3‐CoA and the inhibition of PANK. The sequestration of CoA as C3‐CoA coupled with the inhibition of PANK leads to a cellular deficiency in CoASH. Acetyl‐CoA is also reduced due to the lack of CoASH to support pyruvate dehydrogenase activity. BBP‐671 counteracts that inhibition of PANK leading to an increase in CoASH and restoration of acetyl‐CoA and mitochondrial function. Metabolites that are significantly elevated in PA are shown in red boxes.