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. Author manuscript; available in PMC: 2018 Nov 1.
Published in final edited form as: Prog Retin Eye Res. 2017 Nov 22;64:131–156. doi: 10.1016/j.preteyeres.2017.11.002

Fig. 3. Glucose metabolism and the Warburg effect in the retina.

Fig. 3

(a) Distribution of GLUT1, the main glucose transporter of the retina. (b) Schematic representation of oxidative phosphorylation, anaerobic glycolysis, and aerobic glycolysis (Warburg effect). In the presence of oxygen, differentiated tissues metabolize glucose to pyruvate via glycolysis. Pyruvate is then metabolized in mitochondria by oxidative phosphorylation. The electron transport chain requires oxygen to completely oxidize glucose. When oxygen is scarce, cells redirect pyruvate away from mitochondria to produce lactate (anaerobic glycolysis). Anaerobic glycolysis allows glycolysis to continue by cycling NADH back to NAD+but limits ATP production compared to oxidative phosphorylation. Warburg observed that cancer cells convert most glucose to lactate, irrespective of the presence of oxygen (aerobic glycolysis). The ‘Warburg effect’ is also observed in non cancerous tissues, such as the retina, which, though non proliferative have continuous replacement of outer segments and behave metabolically as “proliferative” cells. Aerobic glycolysis which is less energy efficient may provide building blocks required for growth. In proliferating cells, glucose is in part diverted to biosynthetic pathways upstream of pyruvate production. (c) This schematic summarizes glucose metabolism including glycolysis, oxidative phosphorylation, the pentose phosphate pathway, and glutamine metabolism in “proliferating” cells. Growth factor signaling, such as VEGF, leads to both tyrosine kinase and AKT/PI3K activation. In doing so, growth factors promote glucose uptake and flux through the early part of glycolysis, while inhibiting the late steps; they force glycolytic intermediates towards biosynthetic pathways of macromolecules essential for cell “proliferation” and NADPH production. Metabolic pathways are labeled in purple, and the enzymes controlling critical metabolic steps are shown in blue boxes. Figure modified, with permission, from (Gospe et al., 2010; Vander Heiden et al., 2009).