A model for testing compounds influencing porphyrin synthesis.
The yeast Saccharomyces cerevisiae cultivated semi-anaerobically in a synthetic medium was used as a model to establish (a) total porphyrin synthesis, (b) ratio of intracellular to extracellular porphyrin concentrations. The antimalarials used for the therapy of porphyria cutanea tarda, chloroquine and pyrimethamine, reduced the total synthesis of porphyrins, pyrimethamine being more effective than chloroquine, like in porphyric patients. Both drugs exerted an antagonistic influence on the release of porphyrins from cells. Chloroquine reduced the concentration ratio of porphyrins while pyrimethamine increased it, apparently through inhibition of permeation of porphyrins. Combined treatment with the two compounds may hold promise for the therapy of porphyria cutanea tarda.
D002462:Cell Membrane / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D008954:Models, Biological; D010539:Permeability; D011166:Porphyrins / Q000096:biosynthesis*; D011739:Pyrimethamine / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D011166:Porphyrins; D002738:Chloroquine; D011739:Pyrimethamine