Question

Stimulation of de novo pyrimidine synthesis by growth signaling

through mTOR and S6K1, Ben-Sahra ET AL, Science 2013

1.How does mTORC1 affect lipid and sterol synthesis?

2. How is mTORC1 activated?

3.What 5 metabolites decrease in response to treatment of cells with rapamycin?

4. What pathway had significant in metabolic flux in Tsc2 -/-cells?

5. Describe the data that shows the affect on Tsc-/- cells of long-term sensitivity to rapamycin by the formation of carbamoyl-aspartate. Explain how these findings were confirmed?

6. Explain the results showing that glutamine flux was not affected by rapamycin. From you knowledge of glutamine synthesis and utilization, what is the reason for it not might not being controlled in these transformed cells? Hint think glutamine utilization as a source of αKG.

7. Interpret the Insulin data. How does the analysis of the data in Fig. 4E, Fig. S7A, & Fig. S7D especially show about Insulin?

8. What does the CAD transcription and expression data show about the affect of mTORC1 on CAD?

9. Insulin stimulates the phosphorylation of CAD. Discuss the data and what does this show about control of this pathway?

10. Analyze the data of Figure 4. What do these results indicate?