PCL486H1 Lecture Notes - Lecture 12: Idh1, Succinic Acid, Glutamine
26 Feb 2017
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Heavy isotope-labelled glutamine: m+5 glutamine converted to m+5 glutamate, then into m+5 ketoglutarate. If succinate is derived from glucose, you can m+2 succinate. If you derive it from glutamate, you"ll have m+5: look how different metabolites can enter different pathways /where they came from. Tracking the metabolic destination of carbon using gas-chromatograph/mass-spectrometry gc/ms. They know ecar was going up from the seahorse experiment. Looking at the rate of lactate generation. Compensate for inefficiency of warburg effect by increasing rate of glucose uptake: the increase in atp seen below is likely due to increased glucose uptake (c) In cre+ mice, the glucose is incorporated into lactate much faster than wt (a and b) Produced an onco-metabolite, not seen in cells. Completely new metabolite rather than a shift or alteration of the typical pathway. If you overexpress this mutant idh in cells 2hg levels go up. In wt protein, when over expressed doesn"t produce as large as an effect.
