Carbon dioxide formation mirrors the final carbon oxidation steps of aerobic metabolism in microbial and mammalian cells. As a consequence, Formula: see text dissociation equilibria arise in fermenters by the growing culture. Anaplerotic reactions make use of the abundant Formula: see text levels for refueling citric acid cycle demands and for enabling oxaloacetate-derived products. At the same time, CO2 is released manifold in metabolic reactions via decarboxylation activity. The levels of extracellular Formula: see text depend on cellular activities and physical constraints such as hydrostatic pressures, aeration, and the efficiency of mixing in large-scale bioreactors. Besides, local Formula: see text levels might also act as metabolic inhibitors or transcriptional effectors triggering regulatory events inside the cells. This review gives an overview about fundamental physicochemical properties of Formula: see text in microbial and mammalian cultures effecting cellular physiology, production processes, metabolic activity, and transcriptional regulation.