In this regard, the activation of alternative isotypes of metabolic enzymes such as acetyl-CoA synthases (ACSS1, ACSS2, and ACSS3), aldolase (ALDOA and ALODB), pyruvate kinases (PK) (PKM and PKLR), and mitochondrial C1-tetrahydrofolate dehydrogenases (MTHFD1L/MTHFD2/MTHFD1) are critical determinants in the progression of HCC [177]. Here, PKM is linked to hepatocellular carcinoma.