Chapter 5 - Overflow Metabolism in Human Disease

Abstract

In the first chapter, we alluded to the occurrence of overflow metabolism in cancer and immune responses. Warburg’s early observations on aerobic fermentation highlighted metabolic differences between cancer cells and normal tissues. In turn, Crabtree demonstrated that normal tissues infected with viruses exhibited aerobic fermentation. Aerobic fermentation may happen for different reasons in those contexts. In the immune response to infections, the immune cells manifest a dramatic increase in their proliferation rate, while maintaining functional mitochondria. Cancer cells do not proliferate as fast as activated immune cells, but cancer cells mitochondria have lower horsepower. In either case, the outcome is the same, an obligatory increase in fermentation to sustain the energy demand of cell metabolism. This increase in fermentation is similar to the switch to fermentation metabolism when running beyond the lactate threshold speed. The only difference is the tissue where fermentation has increased. In the following, we adapt the fermentation metabolism model of muscle physiology to other fermenting tissues.