Next, the pyruvate is converted to acetyl-CoA and involved in the oxidative phosphorylation, in mitochondria, to generate 36 ATP molecules per one glucose molecule with CO 2 and H 2O, as byproducts 1, 2. At the initial phase, a glucose molecule undergoes the glycolysis process to produce two ATP, two NADH, and two pyruvate molecules. Glucose metabolism is a binomial process in normal cells. Glucose is the most important energy source for mammalian cells. The proposed model also predicted that the phosphofructokinase-1 and phosphoglucomutase enzymes might play the most important roles in the regulation of the lactate production. This model clearly showed an increase in the lactate concentration during the oxygen depletion. ![]() The main objective was to establish a quantitative relationship between the hypoxia intensity and the intracellular lactate levels and determine the key regulators of the glycolysis pathway. Having capitalized on the computational modeling, in this study, for the first time, we aimed to investigate the effects of hypoxia-induced factor-1 (HIF-1) mediated hypoxia on the magnitude of functional expression of all the enzymes and transporters involved in the glycolysis process. The latter phenomenon can finally lead to the lactate accumulation and pH dysregulation in the tumor microenvironment and subsequently further invasion and metastasis of cancer cells. Glucose metabolism is an important part of this phenomenon, which is associated with changes in the functional expression of transporters and enzymes involved in the glycolysis pathway. The net products of this process are two molecules of ATP produced and two molecules of NADH.In solid tumors, hypoxia can trigger aberrant expression of transcription factors and genes, resulting in abnormal biological functions such as altered energetic pathways in cancer cells. Overall, glycolysis converts one six-carbon molecule of glucose into two three-carbon molecules of pyruvate. An ADP is converted to an ATP in this reaction.Īll of these reactions will happen twice for one molecule of glucose. Phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase. Phosphoglycerate is converted to phosphoenolpyruvate (PEP) by enolase.This reaction releases a water molecule. This step converts an ADP to an ATP.ģ-phosphoglycerate is converted to 2-phosphoglycerate by phosphoglycerate mutase by enzyme glyceraldehyde-3-phosphate dehydrogenase.ġ,3-bisphosphoglycerate is converted to 3-phosphoglycerate by phosphoglycerate kinase. This is a redox reaction in which NAD+ is converted to NADH. Glyceraldehyde-3-phosphate is converted into 1,3-bisphosphoglycerate. In the second half of glycolysis, the three-carbon sugars formed in the first half of the process go through a series of additional transformations, ultimately turning into pyruvate. The two molecules exist in equilibrium, but the equilibrium is “pulled” strongly downward, in the scheme of the diagram above, as glyceraldehyde-3-phosphate is used up. ![]() They are isomers of each other, but only one-glyceraldehyde-3-phosphate-can directly continue through the next steps of glycolysis.ĭHAP is converted into glyceraldehyde-3-phosphate. This step is catalyzed by the enzyme phosphofructokinase.įructose-1,6-bisphosphate splits to form two three-carbon sugars: dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. Glucose-6-phosphate is converted into its isomer, fructose-6-phosphate.Ī phosphate group is transferred from ATP to fructose-6-phosphate, producing fructose-1,6-bisphosphate. ![]() Glucose-6-phosphate is more reactive than glucose. Two ATP are spent to form an unstable sugar with two phosphate groups, which then splits to form 2 three-carbon molecules that are isomers of each other.Ī phosphate group is transferred from ATP to glucose, making glucose-6-phosphate. Microorganisms employ several metabolic pathways to catabolize glucose and other sugars.ĭuring the energy-requiring phase of glycolysis. The Embden-Meyerhof pathway or Glycolysis. Glycolysis Introduction, Pathway, Diagram & Summary Glycolysis
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