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Effect of methotrexate (MTX) on NAD(P) + dehydrogenases of HeLa cells: malic enzyme, 2‐oxoglutarate and isocitrate dehydrogenases
Author(s) -
Caetano Nilce N.,
Campello Annibal P.,
Carnieri Eva G. S.,
Kluppel Maria Lúcia W.,
Oliveira Maria Benigna M.
Publication year - 1997
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/(sici)1099-0844(199712)15:4<259::aid-cbf749>3.0.co;2-d
Subject(s) - isocitrate dehydrogenase , malic enzyme , hela , biochemistry , enzyme , dehydrogenase , lactate dehydrogenase , cytosol , malate dehydrogenase , methotrexate , metabolite , substrate (aquarium) , chemistry , nad+ kinase , biology , cell , ecology , immunology
The effects of methotrexate (MTX) on oxygen uptake by permeabilized HeLa cells were evaluated. MTX did not inhibit state III respiration when the oxidizable substrate was succinate, but when the substrates were 2‐oxoglutarate or isocitrate the respiration decreased about 50 per cent at 1·0 m M concentration of the drug. This effect was explained by inhibition of 2‐oxoglutarate and isocitrate dehydrogenases by MTX. No effect was observed on succinate dehydrogenase. An evaluation of the effects of MTX on malic enzyme activity as measured by pyruvate plus lactate production in intact cells supplied with malate showed a decrease of about 40 per cent in metabolite production using 0·4 m M MTX. HeLa cell malic enzyme, as observed for other tumour cells, is compartmentalized in mitochondria and cytosol, and is another example of a dehydrogenase inhibited by MTX. © 1997 John Wiley & Sons, Ltd.