Glucose is first broken down in the cytoplasm by glycolysis, producing pyruvate and a net gain of 2 ATP and 2 NADH per glucose molecule. If oxygen is present, pyruvate then enters the mitochondria where it is further oxidized in the mitochondrial matrix through the pyruvate dehydrogenase complex and the citric acid cycle, leading to substantial ATP production via oxidative phosphorylation. In the absence of oxygen, pyruvate is converted to lactate in the cytoplasm. Details by step:
- Glycolysis (cytosol): Glucose → 2 pyruvate + 2 ATP (net) + 2 NADH. This pathway functions whether or not oxygen is present, but its fate changes with oxygen availability [biochemical pathways overview].
- Mitochondrial entry (aerobic): Each pyruvate is transported into the mitochondrial matrix and converted to acetyl-CoA, releasing CO2 and generating NADH.
- Citric acid cycle (mitochondrial matrix): Acetyl-CoA is oxidized to CO2, producing NADH, FADH2, and a small amount of ATP (substrate-level).
- Oxidative phosphorylation (inner mitochondrial membrane): NADH and FADH2 donate electrons to the electron transport chain, driving proton pumps that create a proton motive force used by ATP synthase to generate large amounts of ATP from ADP and Pi.
- Anaerobic option (no oxygen): Pyruvate is reduced to lactate by lactate dehydrogenase, regenerating NAD+ needed for glycolysis to continue, yielding a small amount of ATP.
Key takeaways:
- The initial glucose breakdown by glycolysis happens in the cytosol and yields 2 ATP and 2 NADH per glucose (net).
- In the presence of oxygen, mitochondria catabolize pyruvate through the pyruvate dehydrogenase step and the citric acid cycle, followed by oxidative phosphorylation, to produce most of the cell’s ATP.
- Without oxygen, cells rely on glycolysis to produce ATP and convert pyruvate to lactate to regenerate NAD+.
