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Induction of -Aminolevulinic Acid Synthase Activity and Inhibition of Heme Synthesis in Euglena gracilis by N-Methyl Mesoporphyrin IX ¹

Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912

N-Methyl mesoporphyrin IX, an inhibitor of heme synthesis, increases extractable -aminolevulinic acid (ALA) synthase activity when administered to growing cultures of Euglena gracilis Klebs strain Z Pringsheim in micromolar concentrations. Wild-type light-grown green cells and white aplastidic cells exhibited 2.8-fold and 1.8-fold increases, respectively, in ALA synthase activity within five to six hours after incubation with 4 x 10^–6 molar N-methyl mesoporphyrin IX. Protoheme levels were decreased and ⁵⁹Fe incorporation into heme was inhibited by N-methyl mesoporphyrin IX, indicating that, as in animal cells, N-methyl mesoporphyrin IX acts specifically to block iron insertion into protoporphyrin IX. Chlorophyll synthesis in wild-type cells was not affected within the first 6 hours after administration of N-methyl mesoporphyrin IX.

¹ This work was supported by National Science Foundation Grant PCM-8003730 to S.I.B. and by United States Public Health Service Biomedical Research Support Grant 5S07RR07085 to the Division of Biology and Medicine, Brown University.