Figure 2.

Proposed mechanism of urea cycle dysfunction in fibrolamellar hepatocellular carcinoma (fHCC). Under normal condition (A), OTC activity is higher than ODC, so ornithine enters the urea cycle. In fHCC (B), mutation in chromosome 19 led to a chimeric protein DNAJB1-PRACA that leads to increased ODC activity, resulting in an increased utilization of ornithine for polyamine synthesis and a decreased urea cycle function. ch19, chromosome 19; DNAJB1, DnaJ Heat Shock Protein Family (Hsp40) Member B1; PRKACA, Protein Kinase CAMP-Activated Catalytic Subunit Alpha; c-Myc, myelocytomatosis oncogene; ODC, ornithine decarboxylase; OTC, ornithine transcarbamylase.