1. Relationship between tumor-speci

1. Relationship between tumor-specific glucose metabolismand genetic changes. When normal differentiatedtissues are in the presence of oxygen, one glucose moleculecan generate up to 36 ATP molecules. Glycolysis is the primarymetabolic pathway in the cytoplasm that converts glucoseto two pyruvate molecules. This process releases twoATP and two reduced nicotinamide adenine dinucleotide(NADH) molecules. Pyruvate is then transported to the mitochondriaand is converted to an acetyl group that comesalong with coenzyme A to form the acetyl-CoA complex.Acetyl-CoA then joins the Krebs cycle in the mitochondrialmatrix. The net result is one ATP, three NADH andone reduced flavin adenine dinucleotide (FADH2). The electrontransport chains (I, II, III, IV) are electron transportersinserted into the inner mitochondrial membrane that transportelectrons from NADH and FADH2 to oxygen. In thepathway, protons are impelled from the mitochondrialmatrix to the intermembrane space, and oxygen is the finalacceptor for conversion to water molecules. Regarding oxygenreduction, ROS are produced in complex I, II, and III(14). The energy is deposited in the form of a proton gradientbetween the intermembrane space and matrix, and theenergy will finally be converted to ATP (15). The completedprocess results in the yield of 36 ATP molecules. However,under conditions where oxygen is limited, glucose undergoesanaerobic metabolism, which is the partial oxidation ofglucose to pyruvate, and is reduced to lactate (in human) oralcohol (in bacteria). NADH becomes oxidized, and 1-NAD+ is regenerated for glycolysis. Only two ATP moleculesare yielded in anaerobic metabolism. Interestingly, theWarburg effect results in atypical metabolism, indicatingthat cancer cells mostly convert glucose into lactate even inthe presence of oxygen. This characteristic is shared withnormal proliferating cells. The net energy yield in anaerobicglycolysis is two ATP molecules, whereas the yield inoxidative phosphorylation is thirty-six. This observationleads to the paradox: why is the pathway that produces lessATP selected in such high-demand cells and is the Warburg