The use of N-methylprotoporphyrin dimethyl ester to inhibit ferrochelatase in Rhodopseudomonas sphaeroides and its effect in promoting biosynthesis of magnesium tetrapyrroles.
N-Methylprotoporphyrin dimethyl ester inhibits ferrochelatase in isolated membranes of Rhodopseudomonas sphaeroides at low concentrations (around 10 nm). Full inhibition developed after a short lag phase. The inhibition was non-competitive with porphyrin substrate. Addition of inhibitor to growing cultures of Rps. sphaeroides caused a decrease (near 40%) in cytochrome content and a severe inhibition of ferrochelatase; the excretion of haem into the medium by cell suspensions was also severely inhibited. The addition of N-methylprotoporphyrin dimethyl ester to suspensions of photosynthetically competent Rps. sphaeroides Ga caused excretion of Mg-protoporphyrin monomethyl ester. When added to mutants V3 and O1, magnesium divinylphaeoporphyrin a5 monomethyl ester and 2-devinyl-2-hydroxyethylphaeophorbide a were excreted, with maximum effect at around 3 microM-inhibitor in the medium. The results are interpreted to suggest that the inhibitor decreases concentration of intracellular haem, which normally controls the activity of 5-aminolaevulinate synthetase. Unregulated activity of this enzyme leads to overproduction of protoporphyrin, which is diverted to the bacteriochlorophyll pathway. Further control operates at magnesium protoporphyrin ester conversion in normal cells.
D002462:Cell Membrane / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D005294:Ferrochelatase / Q000037:antagonists & inhibitors*; D006418:Heme / Q000378:metabolism; D007700:Kinetics; D008190:Lyases / Q000037:antagonists & inhibitors*; D008274:Magnesium / Q000378:metabolism; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D011758:Pyrroles / Q000096:biosynthesis*; D012242:Rhodobacter sphaeroides / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013053:Spectrophotometry; D045725:Tetrapyrroles
D003580:Cytochromes; D011166:Porphyrins; D011524:Protoporphyrins; D011758:Pyrroles; D045725:Tetrapyrroles; D006418:Heme; C036899:N-methylprotoporphyrin dimethyl ester; D008190:Lyases; D005294:Ferrochelatase; D008274:Magnesium