7.5 The Cori cycle

We have seen in section 3.6 that lactate accumulates in anaerobic glycolysis. Cells producing lactate will release it into the blood. What becomes of it subsequently? It may be taken up by the liver, reoxidized to pyruvate, and fed back into gluconeogenesis. The combination of glycolysis in peripheral tissues with gluconeogenesis in the liver is referred to as the Cori cycle (Figure 7.5-1).

While gluconeogenesis is certainly important in the utilization of lactate generated in the skeletal muscle, most books fail to point out that the two stages of this 'cycle' cannot be active at the same time, for the following reasons:

Under conditions of maximal exercise, liver perfusion is minimized, and the liver itself is quite as anaerobic as the muscle itself. It gets even less oxygen than the muscle does, and without oxygen, the liver cannot regenerate the NAD⁺ needed for turning lactate into pyruvate any more than the muscle could.
Since gluconeogenesis costs more ATP than glycolysis generates (cf. section 7.4), the net energy balance of the Cori cycle will be the expenditure, not the gain of ATP—not too helpful for sustaining maximal exercise.

So, what really happens is that after maximal exercise has stopped, the liver slowly scoops up the lactate that has accumulated in the blood and turns it back into glucose. Thus, the Cori cycle operates asynchronously rather than continuously—it has more similarity with the hog cycle of the agricultural markets than with a regular metabolic cycle such as the TCA.

The Cori cycle does indeed run synchronously with cells such as erythrocytes and thrombocytes, which don't have mitochondria and thus rely completely on anaerobic glycolysis even under aerobic conditions. However, their energy requirements are minuscule compared to those of skeletal muscle.