Effect of methotrexate (MTX) on NAD(P)+ dehydrogenases of HeLa cells: malic enzyme, 2-oxoglutarate and isocitrate dehydrogenases
✍ Scribed by Nilce N. Caetano; Annibal P. Campello; Eva G. S. Carnieri; Maria Lúcia W. Kluppel; Maria Benigna M. Oliveira
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 148 KB
- Volume
- 15
- Category
- Article
- ISSN
- 0263-6484
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✦ Synopsis
The eects 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 mM concentration of the drug. This eect was explained by inhibition of 2-oxoglutarate and isocitrate dehydrogenases by MTX. No eect was observed on succinate dehydrogenase. An evaluation of the eects 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 mM 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.