The metabolic pathway of glycolysis is a series of chemical reactions that convert glucose into pyruvate, generating ATP and NADH in the process. This pathway is essential for generating energy in both normal and cancer cells. However, there are some key differences in the glycolytic pathway between cancer cells and normal cells, which are mainly due to the altered metabolic demands of rapidly proliferating cancer cells. These differences are often referred to as the Warburg effect or aerobic glycolysis.1. Upregulation of glycolysis: Cancer cells have an increased rate of glycolysis compared to normal cells, even in the presence of oxygen. This allows them to generate ATP quickly and provides intermediates for biosynthesis pathways, which are essential for the rapid growth and proliferation of cancer cells.2. Glucose transporters: Cancer cells often overexpress glucose transporters such as GLUT1 and GLUT3 on their cell surface, which allows them to take up glucose at a higher rate than normal cells.3. Enzyme expression and activity: Several enzymes involved in glycolysis are upregulated or have increased activity in cancer cells. These include hexokinase HK , phosphofructokinase PFK , and pyruvate kinase M2 PKM2 .- Hexokinase HK : This enzyme catalyzes the first step of glycolysis, converting glucose to glucose-6-phosphate. Cancer cells often overexpress HK, particularly the HK2 isoform, which has a higher affinity for glucose and is associated with increased glycolytic flux.- Phosphofructokinase PFK : This enzyme catalyzes the rate-limiting step of glycolysis, converting fructose-6-phosphate to fructose-1,6-bisphosphate. Cancer cells often have increased PFK activity, which can be attributed to the upregulation of the PFKFB3 isoform, leading to increased production of fructose-2,6-bisphosphate, a potent allosteric activator of PFK.- Pyruvate kinase M2 PKM2 : This enzyme catalyzes the final step of glycolysis, converting phosphoenolpyruvate to pyruvate. Cancer cells predominantly express the less active PKM2 isoform, which allows for the accumulation of glycolytic intermediates that can be diverted into biosynthetic pathways, such as the pentose phosphate pathway and serine biosynthesis.4. Lactate production and export: In cancer cells, the majority of pyruvate generated through glycolysis is converted to lactate by lactate dehydrogenase A LDHA , even in the presence of oxygen. This lactate is then exported out of the cell by monocarboxylate transporters MCTs , particularly MCT4. This process helps to regenerate NAD+ for glycolysis and maintain a more acidic extracellular environment, which can promote cancer cell invasion and immune evasion.In summary, the metabolic pathway of glycolysis differs between cancer cells and normal cells in terms of upregulation of glycolysis, glucose uptake, enzyme expression and activity, and lactate production and export. These differences are associated with the altered metabolic demands of cancer cells and contribute to their rapid growth and proliferation.