[HTML][HTML] Cancer-associated isocitrate dehydrogenase mutations inactivate NADPH-dependent reductive carboxylation
R Leonardi, C Subramanian, S Jackowski… - Journal of Biological …, 2012 - ASBMB
Isocitrate dehydrogenase (IDH) is a reversible enzyme that catalyzes the NADP+-dependent
oxidative decarboxylation of isocitrate (ICT) to α-ketoglutarate (αKG) and the NADPH/CO 2-
dependent reductive carboxylation of αKG to ICT. Reductive carboxylation by IDH1 was
potently inhibited by NADP+ and, to a lesser extent, by ICT. IDH1 and IDH2 with cancer-
associated mutations at the active site arginines were unable to carry out the reductive
carboxylation of αKG. These mutants were also defective in ICT decarboxylation and …
oxidative decarboxylation of isocitrate (ICT) to α-ketoglutarate (αKG) and the NADPH/CO 2-
dependent reductive carboxylation of αKG to ICT. Reductive carboxylation by IDH1 was
potently inhibited by NADP+ and, to a lesser extent, by ICT. IDH1 and IDH2 with cancer-
associated mutations at the active site arginines were unable to carry out the reductive
carboxylation of αKG. These mutants were also defective in ICT decarboxylation and …