Energy from sugars: glycolysis

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GlcLandscape

The first catabolic pathway we will analyze will clarify how we can extract energy from glucose and other sugars through an oxidative process. Glycolysis is a series of enzyme-catalyzed reactions that ultimately convert one molecule of glucose into two molecules of pyruvate (pyruvic acid). In the process, energy is released and used to synthesize two ATP molecules. Also, NAD+ is reduced to two NADH molecules.

The study of glycolysis will put all the general concepts discussed in the introductory lecture into real-life examples. You will see how group-transfer reactions are used to trap glucose in the cell and to destabilize the molecule. Then a series of rearrangements and cleavage of C-C bonds will lead to the formation of two three-carbon atom molecules. Finally, these molecules will be used to transfer phosphate groups to ADP, yielding ATP. The final metabolite, pyruvate, may have different fates according to the cell type and needs. Yeast, for instance, will use it to produce ethanol!

Deficiency in the glycolytic enzymes will cause disease. No surprise, since glucose is the major fuel for most types of cells in our body. However, some cells are more sensitive than others to glycolytic deficiency, and this is because they cannot extract energy from other nutrients, such as fat. One example are the red blood cells (RBCs, erythrocytes), that can obtain energy only from glycolysis. When one glycolytic enzyme is deficient, the most typical clinical manifestation is anemia: RBCs die of exhaustion. However, some glycolytic enzyme deficiencies can also affect muscles, the nervous system, or the immune system.

Note that cancer cells have normally an elevated glycolytic metabolism, since they require energy to synthesize nucleotides and DNA for cell proliferation. Hmmm, could inhibition of glycolysis be a target for cancer chemotherapy, I wonder…? Well, while you ponder this possibility let me break you the news that arsenic poisoning acts also through inhibition of a glycolytic enzyme.

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