The NAD⁺/NADH balance of a cell is critical. Cells require sufficient quantities of NAD⁺ to accept electrons produced in oxidative reactions. In the absence of NAD⁺, oxidative reactions in the cell can be completely halted. Since oxidation is the primary source of cellular energy for most non-plant species, the lack of NAD⁺ can have dire consequences for cells.

Reaction #6 in glycolysis requires NAD⁺. Lack of this substrate can bring glycolysis to a halt.

When the electron transport system (ETS) and oxidative phosphorylation (OxPhos) are operating, NADH is recycled back to NAD⁺ when NADH dumps electrons into the electron transport system (Figure 13.1).

If OxPhos is stopped for some reason (e.g., under heavy exercise the blood is unable to deliver oxygen fast enough to keep OxPhos occurring), then ETS stops and NADH cannot be recycled at the mitochondrion.

Without an alternative means of recycling NADH to NAD⁺, the cell would not be able to generate ATP from glycolysis and would die.

To avoid this scenario, fermentation may occur.

Fermentation is a non-oxidative process because the product(s) of fermentation are in the same oxidative state as the starting materials.

For example, in lactate fermentation (animal cells), pyruvate is converted to lactate using the electrons of NADH, forming NAD⁺. Lactate is in the same oxidative state as glucose, the starting material of glycolysis. Yeast go through ethanolic fermentation for the same reason with the same result.