Heme-biosynthetic enzyme activities and porphyrin accumulation in normal liver and hepatoma cell lines of rat.

The activities of four heme-biosynthetic enzymes, delta-aminolevulinic acid (ALA) synthase, ALA dehydratase, porphobilogen (PBG) deaminase, and ferrochelatase, were studied in five epithelial cell lines of normal rat liver origin (RL, RLC-10, RLC-24, M, Culb-TC) and five cell lines derived from Yoshida ascites hepatoma (JTC-1, JTC-2, JTC-15, JTC-16, JTC-24). The JTC series of hepatoma-derived cell lines exhibited decreased ALA synthase activity and increased ALA dehydratase activity, although the activities of all four enzymes and the Km values for their respective substrates varied widely from one cell line to another, a finding suggesting that specific regulatory mechanisms for porphyrin metabolism might operate in each cell type. M cells, which were transformed by 4-dimethylaminoazobenzene in vitro, gave the most abnormal Km values of heme-biosynthetic enzymes among all the cell lines studies, and were found to accumulate hematoporphyrin derivative (HpD).