3.6 Function of glycolysis under anaerobic conditions

Two molecules of ATP are expended in the initial phosphorylation steps (1 and 3 in Figure 3.3-1). ATP is gained in steps 7 and 10. Since all of the steps from 6 to 10 occur twice per molecule of glucose, the net balance is a gain of two moles of ATP per mole of glucose—a very modest number indeed, considering that the overall yield in complete oxidative degradation is above 30 moles of ATP. Still, degradation of glucose to pyruvate is a viable source of energy, and it is the major one that operates in our tissues while oxygen is in short supply, as in skeletal muscle during maximal exercise such as a 100 meter dash.

To make 'anaerobic' (= oxygen-free) glycolysis feasible, we have to solve one problem. In the glyceraldehyde-3-phosphate dehydrogenase reaction, a molecule of NAD⁺ is consumed and converted to NADH. Under aerobic conditions, that is when oxygen is available, NADH is reverted to NAD⁺ in the respiratory chain. However, under anaerobic conditions, we need another means to regenerate NAD⁺.

This problem is overcome by the hydrogenation of pyruvate to lactate by lactate dehydrogenase (Figure 3.6-1a). Even then, as you know from experience, this maximal level of exertion cannot be kept up for long. We will soon have to slow down as both exhaustion and pain set in. Exhaustion is due to the depletion of ATP and of glucose, while pain is due to the accumulation of lactate in the tissues and the blood¹.

Some cells in the human body, most notably the erythrocytes (red blood cells), rely entirely on anaerobic glycolysis for ATP production, since they lack the ability to oxidize pyruvate. Anaerobic glycolysis is a common pathway of energy production not only in animals but also in microbes, for example in baker's yeast. These face the same problems as human cells do, that is they need to regenerate NAD⁺ and dispose of the acid. The latter task is even more pressing for them than for our us, since they don't have a blood circulation to carry away, dilute and buffer the excess acid. One effective strategy, then, is to chemically degrade the acid. This is the biological purpose of ethanolic fermentation (Figure 3.6-1b).

1: Measurement of the blood lactate concentration is performed in sports medicine to gauge the capacity of a trained athlete to sustain aerobic rather than anaerobic metabolism during prolonged exertion. The anatomical correlate of endurance is not so much the build-up of muscle tissue but the extent of its vascularization, i.e. the abundance of capillaries in the tissue. A high density of capillaries ensures good oxygen supply.