Coupling of Energy Supply and Energy Demand in Isolated Goldfish Hepatocytes

Gerhard Krumschnabel, Pablo J. Schwarzbaum, Wolfgang Wieser

Physiological Zoology · 1994 · 46 citations · 12 references

Concepts

TL;DR

The mismatch between ATP supply and demand in hepatocytes reflects flexible energy allocation under limiting conditions. The study examined metabolic energy allocation in isolated goldfish hepatocytes under varying supply and demand conditions. Blocking glycolysis reduced Na⁺/K⁺‑ATPase activity and ATP concentration, effects reversible by pyruvate/malate; the pump contributed 15–25% of oxygen consumption and 50–90% of anaerobic load, and its inhibition immediately lowered oxidative output but did not alter lactate production under glycolytic restriction, with ATP falling to a new steady state within 30 min and remaining stable for at least an hour.

Abstract

The allocation of metabolic energy under fluctuating conditions of supply and demand was studied in isolated goldfish hepatocytes. Inhibition of glycolytic ATP production resulted in a decrease in the activity of one of the major ATP consuming components of cellular energy budgets, the sodium pump ((Na⁺, K⁺)-ATPase), because of the removal of substrates for the trichloroacetic acid (TCA) cycle. This was confirmed through restoration of activity to control levels by adding pyruvate and malate to the suspension. Ouabain-sensitive oxygen consumption constituted a fairly constant fraction of 15% to 25% of total oxygen consumption, whereas the relative load exerted by the pump on anaerobic energy metabolism (on the basis of measurements of Rb⁺ flux and lactate production) was much higher, ranging from 90% to 50% during the experimental period. Moreover, when pump activity was inhibited by the addition of ouabain, oxidative energy output decreased immediately, whereas under the restricted conditions of glycolytic energy supply a corresponding ouabain-sensitive component of lactate production was not observed. Such an apparent mismatch between supply and demand ofATP is interpreted as reflecting the flexibility of energy allocation under energy-limiting conditions. When ATP production was reduced by inhibiting either glycolysis or oxidative phosphorylation, the concentration of ATP in the hepatocytes dropped within 30 min from the control steady state to a new, lower, steady state that was maintained for at least 60 min.

References

12