Tumour metabolism

jambomber's version from 2015-05-13 16:37


Question Answer
What are the effects of HIF expression?Up all bar PGM, Up GLut1+3, inhibition of PDH by PDK1,COx 412- Cox411, TFAm red biogen , Myc upreg
Why does HIF upreg a higher affinity COX?Increased oxygen scavenging to deal with a reduced respiratory chain generation ROS
Why is oxygen needed at all?Absolutely req for the biosynthesis of cholesterol- therefore important t consevr
Which oncogenes upreg HIFRas
What does acidic conditons select for?Motile cells and metastasis
which metabollic enzymes function as tumour supressors?Fumerate + Malate dehydrogenases. When lost enable buildup of biosynth intermdeidates ie Succinate
What is the oncometabolite? What forms it? Where2hydoygluterate- mutations in ID1 isocitrate dehydrogenase Brain remours. Overwhelm the normal degradation process
How does 2HG enable canaceer?Inhibition of DNA+ Histone demethylases Altering gene expression and activates prolylhdroxylaes transfoming Asrocytes
Why does 2HG inhibit the enzymes it does?Diozygenases utilise A keto as a substrate
what percentage of cancers is Myc upreg in? how does it feed into metabolism70% - converges with HIF to upreg gly enzymes and biosynthetic pathways
How do MYC and HIF oppose one anotherUP and downregulate mitochondrial biogen respectively
Where does half of tumour acidity come from?Upregulation of carbonic anhydrase and conversion of CO2 from pyruvate oxidation. Tumour cells defective in glycolysis are still acidic
What does glutamine serve as? What is the evidence for thisAn anapleourotic substrate NADPH source. Labelled with 3-13 C. Found in TCA cycle intermediates
How does MYC increase glutamine utilisation?Through an miRNA
What is anapleurosis?Replenishing the TCA cycle with
What is the dual role of P53 in cancer metabolism?Under low stress p53 Upregulates antioxidants by diverting flux through PPP Under high Stress it inhibis the antioxidant genes through PGM
What did the Metallo paper suggest?Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. show that human cells use reductive metabolism of α-ketoglutarate to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived α-ketoglutarate for de novo lipogenesis
How does TIGAR influence metabolismDiverts flux by deg F2,6Bp a feed forward activator of downstream glycolysis