Regulation of cellular metabolism by intracellular phosphate

Abstract

1. Incubation of liver cell suspensions with 10 mM glycerol or 10 mM fructose caused a decrease in intracellular [P i] and a fall in the [ ATP] [ ADP] while the respiratory rate, the redox state of the intramitochondrial NAD couple, and the [ ATP] [ ADP] · [ P i ] remained essentially unaltered. 2. The concentration of intracellular phosphate in yeast Candida utilis was found to be dependent on phosphate concentration in the growth medium: it was 25–30 μmol/g wet weight in cells grown in the presence of 50 mM P i, 10–12 μmol/g wet weight in cells grown in 5 mM P i, and 3–4 μmol/g wet weight in cells grown with 1 mM P i. 3. The [ ATP] [ ADP] ratios were found to be highest in yeast cells grown in the presence of 50 mM P i (⩾ 30) and lowest in cells grown with 1 mM P i (8–9). The increase in [ ATP] [ ADP] was due to an increase in [ATP]. 4. The endogenous levels of glucose 6-phosphate in washed and aerated cells were lowest in cells grown in the presence of 50 mM P i and highest in those grown in the presence of 1 mM P i. A suggestion is made that the high intracellular [P i] stimulates phosphorolytic breakdown of glycogen and depletes the cellular stores of this substrate. 5. It is postulated that the cellular respiratory rate and the NADH generation rate are regulated by [ ATP] [ ADP] · [ P i ] and not by the “energy charge” as defined by Atkinson (Biochemistry 7, 4030–4034, 1968). 6. The concentration of intracellular [P i] is implicated as an important contributor to the regulatory mechanisms of cellular metabolism.