Treatment
with hydroxycitrate, a potential anticancer drug
that targets ACLY, results in decreased cholesterol and fatty acid
synthesis in HepG2 cells. – ACLY: ATP-citrate
lyase HMGCR: 3-hydroxy-3-methylglutaryl-CoA
reductase PDH: pyruvate dehydrogenase
IDH1: isocitrate dehydrogenase 1
IDH2: isocitrate dehydrogenase 2
GLS1: glutaminase 1 GLS2:
glutaminase 2 ACACA: acetyl-CoA
carboxylase FASN: fatty acid
synthase
1) You have been assigned a metabolic
labeling project to study the effect of
hydroxycitrate on fatty acid and cholesterol
biosynthesis. The only precursors available in your laboratory is
14C-mevalonate.
A) Is 14C-mevalonate useful for
your experiments? Explain.
B) If you have the option to buy a
14C-precursor for your experiments, which one would you
choose?
Glucose ECM Palmitate_Complex FAs Glucose FASN Glucose-6-phosphate Cytosol Malonyl CoA Acetyl CoA Pyruvate Lactate Fatty acid synthesis pathway ACACA Glycolysis ACLY Acetylation reactions Pyruvate Citrate Acetyl CoA PDH Mevalonate pathway Acetyl CoA HMG-CoA Citrate Citrate OAA Citrate HMGCR synthase Mevalonate Isocitrate TCA cycle IDH1 Geranyl-PP 0 α-KG α-KG Isocitrate IDH2 GLS1 Citrate Glutamate FPP Glutamate Protein prenylation Glutamine metabolism GLS2 Squalene GG-PP Glutamine Glutamine Glutamine metabolism Cholesterol © 2012 American Association for Cancer Research Cancer Research Reviews





