Methotrexate: studies on cellular metabolism. II--Effects on mitochondrial oxidative metabolism and ion transport.
Effects of methotrexate (MTX) on mitochondrial oxidative metabolism and ion transport were studied. MTX decreases the membrane potential (delta psi) upon energization of the mitochondrial membrane by NAD+-linked substrates and decreases the amplitude and velocity of swelling induced by glutamate and alpha-ketoglutarate. MTX also has an inhibitory effect on the activities of the oxidation enzymes of NAD+-linked substrates without interfering with the oxidation systems of FAD-linked substrates. The effects of MTX could be interpreted as a consequence of a decrease in the ionic conductivity of the mitochondrial inner membrane.
Departamento de Bioquímica Universidade Federal do Paraná, Brasil.
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Yamamoto
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LC
Lopes
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Campello
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Klüppel
D000818:Animals; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D066298:In Vitro Techniques; D007477:Ions / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008727:Methotrexate / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013385:Succinate Dehydrogenase / Q000378:metabolism
D007477:Ions; D009243:NAD; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D007655:Ketoglutarate Dehydrogenase Complex; D013385:Succinate Dehydrogenase; D005969:Glutamate Dehydrogenase; D008727:Methotrexate