Glycolysis is the first major pathway of cellular glucose metabolism. It occurs in the cytoplasm of virtually all living cells and converts one molecule of glucose into two molecules of pyruvate, producing a net gain of ATP and NADH.
The Phases of Glycolysis
- Energy Investment Phase
The first half of glycolysis uses two ATP molecules to phosphorylate glucose, trapping it inside the cell. Glucose is converted to glucose-6-phosphate, then to fructose-6-phosphate, and finally to fructose-1,6-bisphosphate. This six-carbon sugar is then split into two three-carbon molecules: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P).
- Energy Payoff Phase
The second half of glycolysis generates energy. Each G3P molecule is oxidized and phosphorylated, producing 1,3-bisphosphoglycerate. The high-energy phosphate groups are then transferred to ADP to produce ATP. Through a series of steps, each G3P is converted to pyruvate, producing two ATP and one NADH per G3P.
- Net Yield
Starting from one glucose molecule, glycolysis produces:
- 2 ATP (net, after subtracting the 2 used in the investment phase)
- 2 NADH
- 2 pyruvate molecules
- Regulation
Glycolysis is regulated at three key irreversible steps. Phosphofructokinase-1 (PFK-1) is the most important regulatory enzyme. It is activated by AMP and ADP (low energy signals) and inhibited by ATP and citrate (high energy signals).
- Fate of Pyruvate
Pyruvate can follow different paths depending on oxygen availability. Under aerobic conditions, it enters the mitochondria and is converted to acetyl-CoA for the citric acid cycle. Under anaerobic conditions, it is converted to lactate in animals or ethanol in yeast.
