“Fire burn and cauldron bubble” (W. Shakespeare): what the calorimetric–respirometric (CR) ratio does for our understanding of cells?

Abstract

In this paper, it has been shown that the existence of anaerobic pathways under aerobic conditions is not always due to poor environmental conditions. There are two sources of lactate in cultured cells, oxidative glutaminolysis and reductive glycolysis. Only the latter is measured in the CR ratio as a value more negative than the oxycaloric equivalent for the relevant catabolic substrate. The validity of the value for the CR ratio can be determined by Mayer’s enthalpy balance method. Highly exothermic ratios are no reflection of thermodynamic efficiency but in many cases indicate the need for ATP not supplied by, or insufficiently available from, oxidative phosphorylation. For other types of cell grown in culture, a highly exothermic CR ratio is due to the fact that there are not sufficient quantities of the appropriate anabolic precursors in the culture medium. Then, biosynthetic precursors must be constructed from substrates using the catabolic pathways and this leads to the reduction of pyruvate in order to conserve NAD +. An on-line measurement of the CR ratio would monitor cell growth and could be used to control fed-batch cultures.