Glycolysis and fermentation

Glycolysis (also called the Embden-Meyerhof-Parnas pathway) breaks one glucose into two pyruvate. It happens in the cytosol of all cells and does not need oxygen. It has ten steps. The first part invests energy:

• Hexokinase adds a phosphate to glucose, making glucose-6-phosphate (using ATP).
• An isomerase turns it into fructose-6-phosphate.
• Phosphofructokinase (PFK) adds a second phosphate, making fructose-1,6-bisphosphate (using ATP).
• Aldolase splits it into two 3-carbon sugars (trioses).

The second part earns energy. Glyceraldehyde-3-phosphate is oxidised, turning NAD⁺ into NADH. Two enzymes, phosphoglycerate kinase and pyruvate kinase, each make ATP directly from ADP: this is substrate-level phosphorylation. Phosphoglycerate mutase and enolase work in between.

Three steps cannot run backwards and are the control points: steps 1, 3 and 10, catalysed by hexokinase, PFK and pyruvate kinase. Per glucose: 4 ATP made, 2 used, so a net gain of 2 ATP, plus 2 NADH and 2 pyruvate.

Without oxygen, the cell must turn NADH back into NAD⁺ so glycolysis can continue:

• In muscle, pyruvate is reduced to lactate by lactate dehydrogenase (homolactic fermentation).
• In yeast, pyruvate decarboxylase (which needs TPP) removes CO₂ to make acetaldehyde, which is reduced to ethanol (alcoholic fermentation).

Either way, only 2 ATP per glucose.

With oxygen, pyruvate enters the mitochondria, where the pyruvate dehydrogenase complex (needing TPP, FAD, NAD⁺ and lipoamide) turns it into acetyl CoA and CO₂. This links glycolysis to the citric acid cycle.