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Effect of CO₂ Concentration on Intracellular pH and on Glycogen Synthesis from Glycerol and Glucose in Isolated Perfused Rat Liver

From the ¹ From the Department of Biochemistry, St. Louis University School of Medicine, St. Louis, Missouri 63104

The effect of variation of extracellular total CO₂ concentration at constant pH on intracellular pH and total intracellular CO₂ content and on the conversion of glycerol-1,3-¹⁴C and glucose uniformly labeled with ¹⁴C to glycogen in perfused rat liver has been studied.

The concentration of perfusate CO₂ was varied from 8 to 40 mm while pH was maintained between 7.4 and 7.5. At the end of a 60-min perfusion period with perfusate of either CO₂ concentration, the intracellular pH remained constant in the range of pH 7.0 to 7.1. Intracellular total CO₂ content followed the changes in extracellular total CO₂ content but was generally 25% lower than the extracellular concentration. Under similar perfusion conditions, liver glycogen content was increased 30 to 60% and glycerol-1,3-¹⁴C conversion to glycogen by 90 to 100% by perfusion with an average total CO₂ concentration of 33 mm as compared to 9 mm total CO₂ in the presence of 13 mm glycerol and 15 mm glucose as substrate. When the only added substrate was glucose adjusted to 5.6 mm initially, glycogen content was not markedly altered by the CO₂ content of the perfusate, but the conversion of glucose uniformly labeled with ¹⁴C to glycogen was increased 90% over control values when the liver was perfused the 1st hour with perfusate containing 11 mm CO₂ followed by perfusion the 2nd hour with 34 mm CO₂.

These results suggest that variation in extracellular total CO₂ concentration within physiological limits does produce alterations in glycogen metabolism by variation of total intracellular CO₂ concentration and not by variation in the average intracellular pH. The results suggest that total intracellular CO₂ concentration may be an important physiological regulator of carbohydrate metabolism.

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