Does mTOR increase glycolysis?
The activity of glycolytic enzyme is elevated in an mTORC1-dependent manner in the TSC-deficient cells. Activated mTOR stimulates HIF-1α and coordinately induces the expression of several enzymes for glucose metabolism, including glucose transporters, HK and LDH [32, 40].
What does rapamycin do to cells?
The target of rapamycin (TOR) is an evolutionarily conserved kinase that integrates signals from nutrients (amino acids and energy) and growth factors (in higher eukaryotes) to regulate cell growth and cell cycle progression coordinately.
How does mTOR regulate metabolism?
mTORC1 regulates hepatic lipid metabolism mainly through SREBP1, the master regulator of lipid synthesis. It is initially synthesized as an inactive precursor and localized in the ER. In response to the insulin signaling, SREBP1 is cleaved and transported to the nucleus to induce lipogenic gene expression.
How does mTOR increase protein synthesis?
mTORC1 controls protein synthesis by activating S6 kinase 1 (S6K1) and inhibiting 4E-binding protein 1 (4EBP1) (Ma and Blenis, 2009).
Does glycosylation of rapamycin reduce cytotoxicity and antifungal activity?
The glycosylation remarkably improved water solubility and almost completely abolished cytotoxicity but simultaneously attenuated the antifungal, antitumor, and immunosuppression bioactivities of rapamycin. We found the glycosylation at C-40 had less effect on the bioactivities than that at C-28.
Does rapamycin up-regulate AKT phosphorylation in breast cancer cells?
Rapamycin treatment of breast cancer cell lines MCF-7 and MDA-MB-468 and the prostate cancer cell line DU-145 (PTEN wild type) all resulted in a significant up-regulation of Akt phosphorylation on S473 [ 147 ]. Akt activation in cancer cells is an unfavorable effect of mTORC1 inhibition as Akt promotes survival and proliferation [ 147 ].
What is rapamycin (sirolimus)?
Rapamycin (sirolimus) is the first mTOR inhibitor discovered as a naturally occurring compound purified from the bacterium Steptomyces hygroscopicus.
What is the last step of glycolysis catalyzed by PK?
This last step of glycolysis is catalyzed by PK (pyruvate kinase).20PK is a very important key enzyme of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP, yielding one molecule of pyruvate and one molecule of ATP.