The metabolic profile of cancer cells differs significantly from that of healthy cells. This altered metabolism, known as the Warburg effect, is characterized by increased glucose uptake, enhanced glycolysis, and reduced oxidative phosphorylation, even in the presence of oxygen. The key metabolic pathways and enzymes that contribute to these differences include:1. Glycolysis: Cancer cells have an increased rate of glycolysis, which is the breakdown of glucose into pyruvate. This process generates ATP and provides metabolic intermediates for the synthesis of nucleotides, amino acids, and lipids. Key enzymes involved in glycolysis include hexokinase HK , phosphofructokinase-1 PFK-1 , and pyruvate kinase M2 PKM2 .2. Glutaminolysis: Cancer cells have an increased reliance on glutamine, an amino acid that serves as a major source of carbon and nitrogen for the synthesis of nucleotides, amino acids, and lipids. Glutaminolysis is the process by which glutamine is converted into -ketoglutarate, which can then enter the tricarboxylic acid TCA cycle. Key enzymes involved in glutaminolysis include glutaminase GLS and glutamate dehydrogenase GLUD .3. Pentose phosphate pathway PPP : The PPP is a parallel pathway to glycolysis that generates ribose-5-phosphate for nucleotide synthesis and NADPH for reductive biosynthesis and antioxidant defense. Cancer cells often have an increased flux through the PPP to support their rapid proliferation. Key enzymes involved in the PPP include glucose-6-phosphate dehydrogenase G6PD and 6-phosphogluconate dehydrogenase 6PGD .4. Lipid metabolism: Cancer cells have an increased demand for lipids to support membrane synthesis and signaling. They often upregulate de novo lipid synthesis pathways and rely on exogenous lipid uptake. Key enzymes involved in lipid metabolism include fatty acid synthase FASN , acetyl-CoA carboxylase ACC , and ATP-citrate lyase ACLY .5. One-carbon metabolism: One-carbon metabolism is essential for the synthesis of nucleotides, amino acids, and lipids, as well as for epigenetic regulation. Cancer cells often have an increased demand for one-carbon units and upregulate enzymes involved in one-carbon metabolism, such as serine hydroxymethyltransferase SHMT , methylenetetrahydrofolate dehydrogenase MTHFD , and methionine adenosyltransferase MAT .6. Mitochondrial metabolism: Although cancer cells often exhibit reduced oxidative phosphorylation, they still rely on mitochondrial metabolism for the synthesis of TCA cycle intermediates and the generation of reactive oxygen species ROS . Key enzymes involved in mitochondrial metabolism include pyruvate dehydrogenase PDH , isocitrate dehydrogenase IDH , and succinate dehydrogenase SDH .These metabolic alterations in cancer cells provide potential targets for cancer therapy. By inhibiting key enzymes or pathways, it may be possible to disrupt the metabolic requirements of cancer cells and selectively target their growth and survival.