口腔种植学精品教学（中山大学）metabolism.pptVIP

metabolism wjc Metabolism in Quiescent versus Proliferating Cells To survive under such conditions, differentiated cells adopt a catabolic metabolism focused on maximizing the efficiency of ATP production from limited nutrients In contrast, when growth factors are abundant, cells increase their nutrient uptake and adopt an anabolic metabolism In cancer cells, the instructional signaling pathways downstream of growth factor receptors can be constitutively activated in the absence of extracellular growth factors. Metabolism in Quiescent versus Proliferating Cells: BothUse Mitochondria Altered Metabolism Is a Direct Responseto Growth-Factor Signaling The traditional cancer model The demand for free energy to sustain transcription and translation drives a decrease in the ATP:ADP ratio, leading to subsequent allosteric effects on rate-limiting metabolic enzymes In this supply-based model Changes in metabolic fluxes occur in primary response to growth-factor signaling, independent of changes in ATP and other mechanisms worked out by early biochemists Altered Metabolism Is a Direct Responseto Growth-Factor Signaling views 1.In contrast to the catabolic metabolism of differentiated cells, this anabolic metabolism fundamental to cell growth and proliferation is not focused on maximizing ATP yield. 2.Rather than ATP, proliferating cells are in much greater need of reduced carbon and reduced nitrogen, as well as cytosolic NADPH for reductive biosynthetic reactions. 3. In fact, most cancer cells and proliferating normal cells still derive a significant fraction of their ATP through oxidative phosphorylation. However, in proliferating cells, in contrast to quiescent cells, this oxidative phosphorylation-dependent production of ATP appears secondary to the use of mitochondrial enzymes in the synthesis of anabolic precursors. PI3K/Akt/mTORC1 Activation: Driving AnabolicMetabolism and Tumorigenesis by ReprogrammingMitochondria Activation of the PI3K/Akt pathway is p