7.2 Glycolysis: steps, regulation, and energy yield

Glycolysis is the first step in breaking down glucose for energy. It's a series of 10 reactions that happen in your cells, turning one glucose into two pyruvate molecules. This process is super important for keeping you alive and kicking.

The cool thing about glycolysis is it doesn't need oxygen. It happens in two phases: prep and payoff. You start with glucose, add some phosphates, split it in half, and end up with pyruvate. Along the way, you make some ATP and NADH for energy.

Overview of Glycolysis

Glucose Breakdown Process

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• Glycolysis is a metabolic pathway that breaks down glucose into two pyruvate molecules
• Occurs in the cytosol of cells and does not require oxygen (anaerobic process)
• Consists of a series of 10 enzyme-catalyzed reactions divided into two phases: the preparatory phase and the payoff phase
• Glucose is first phosphorylated to form glucose-6-phosphate, an important regulatory step that traps glucose inside the cell

Key Intermediates

• Glucose-6-phosphate is an intermediate formed by the phosphorylation of glucose in the first step of glycolysis
• Fructose-1,6-bisphosphate is a key intermediate formed by the phosphorylation of fructose-6-phosphate by phosphofructokinase
• Splitting of fructose-1,6-bisphosphate into two three-carbon molecules (glyceraldehyde-3-phosphate and dihydroxyacetone phosphate) marks the end of the preparatory phase
• Pyruvate is the final product of glycolysis, formed by the dephosphorylation of phosphoenolpyruvate in the last step of the payoff phase

Enzymes and Regulation

Key Regulatory Enzymes

• Hexokinase catalyzes the first step of glycolysis, the phosphorylation of glucose to glucose-6-phosphate
• Phosphofructokinase catalyzes the third step, the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, and is a key regulatory enzyme in glycolysis
• Pyruvate kinase catalyzes the final step, the dephosphorylation of phosphoenolpyruvate to pyruvate, and is also a key regulatory enzyme

Allosteric Regulation

• Allosteric regulation involves the binding of effectors (activators or inhibitors) to enzymes at sites other than the active site, modulating their activity
• Phosphofructokinase is allosterically inhibited by high levels of ATP and citrate, indicating an abundance of energy and biosynthetic precursors
• Phosphofructokinase is allosterically activated by AMP and fructose-2,6-bisphosphate, signaling a need for increased energy production
• Pyruvate kinase is allosterically inhibited by ATP and alanine, while activated by fructose-1,6-bisphosphate, coupling its activity to the energy state of the cell and the flux through glycolysis

Energy Production

ATP and NADH Generation

• ATP (adenosine triphosphate) is the primary energy currency of the cell, and glycolysis generates a net gain of 2 ATP per glucose molecule
• NADH (reduced nicotinamide adenine dinucleotide) is an electron carrier that is generated during glycolysis and can be used to produce ATP in the electron transport chain (oxidative phosphorylation)
• Glycolysis produces a net gain of 2 NADH per glucose molecule, which can yield additional ATP in the mitochondria (approximately 3-5 ATP per NADH)

Substrate-Level Phosphorylation

• Substrate-level phosphorylation is the direct transfer of a phosphate group from a high-energy substrate to ADP, forming ATP
• In glycolysis, substrate-level phosphorylation occurs in two steps: the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate and the conversion of phosphoenolpyruvate to pyruvate
• Each of these steps generates 2 ATP, resulting in a total of 4 ATP produced by substrate-level phosphorylation (2 ATP per triose phosphate, with 2 triose phosphates formed per glucose)

Net Energy Yield

• The net energy yield of glycolysis is 2 ATP and 2 NADH per glucose molecule
• This accounts for the 2 ATP consumed in the preparatory phase (priming steps) and the 4 ATP produced by substrate-level phosphorylation in the payoff phase
• The 2 NADH generated can be further oxidized in the mitochondria to yield additional ATP (approximately 6-10 ATP), increasing the total energy yield of glycolysis to 8-12 ATP per glucose molecule under aerobic conditions