The Metabolism of Acetate in the Perfused Hind‐Quarter of the Rat

Abstract

The elimination kinetics of acetate, the main end product of ethanol metabolism in the liver and the influence of acetate oxidation on the redox- and energy state of the isolated perfused hind-quarter of the rat were studied. The rate of acetate uptake increased with increasing initial concentration of acetate in the perfusion medium, suggesting that the plasma level of free acetate may be one factor in the regulation of acetate uptake in the skeletal muscle. Addition of acetate as a single dose did not affect the net production of lactate or the uptake of glucose. In continuous infusion experiments at a constant concentration of 2 mM of acetate in the medium, the lactate/pyruvate ratio was unaffected in the medium and in the muscle tissue. Addition of acetate did not affect the oxygen uptake. Experiments with 14-C-acetate showed that about 50% of added radioactivity was found in form of 14-CO2 accounting for 25 to 45% of the oxidative metabolism in the muscle tissue. It was calculated that about 25% of the acetate produced in the liver during ethanol oxidation can be consumed in the resting, perfused hind-quarter of the rat. The tissue content of high-energy phosphate compounds was not significantly affected by acetate.

In vivo enzymatic activity of acetylCoA synthetase in skeletal muscle revealed by 13C turnover from hyperpolarized [1-13C]acetate to [1-13C]acetylcarnitine

“…The plasma acetate concentrations used in the current study (1.8-15.1 mM) have been previously shown to linearly scale with the uptake of acetate in skeletal muscle tissue and thus with the cellular acetate concentration [17,18]. This implies that the kinetic parameters extracted from the in vivo real-time measurements presented herein are independent of processes related to membrane transport since acetate uptake by resting skeletal muscle is proportional to the arterial concentration.…”

“…It was estimated that the injected hyperpolarized acetate doses resulted in a plasma acetate concentration ranging from 1.8 to 15.0 mM [32]. Using a previously reported relation between plasma and tissue acetate concentration in rat skeletal muscle [17], it was estimated that the tissue acetate concentration ranged from 0.12 to 1 mM. To determine k ACS from the system of coupled equations defined by Eqs.…”

“…The uptake of acetate by skeletal muscle tissue as a function of the arterial concentration is described in [17,18]. Acetate transport across the cellular membrane occurs by facilitated diffusion, and thus net transport of acetate between the plasma and the tissue depends on the concentration gradient.…”

“…Its oxidation has been deemed significant since it is rapidly cleared from the blood if injected in vivo or generated from precursors such as ethanol in the liver [16]. Acetate uptake by resting skeletal muscle is driven by a concentration gradient and is proportional to the plasma concentration [17,18]. In a single passage of blood, half of the acetate presented to the tissue was removed by the muscle tissue indicating a high affinity for acetate [5].…”

Plasma acetate turnover and oxidation.

“…Unlike the gastrointestinal tract, the production of plasma acetate by both the liver and leg appeared to be dictated by the arterial plasma acetate concentration. Acetate uptake by the rat hind quarter (25) has been found to be dependent on the level of acetate in the perfusion medium and, in addition, Buckley and Williamson (26) have shown that rat liver adds acetate to the hepatic venous blood when the PV concentration is below 0.2 mM. The effect of arterial concentration on the uptake or output of a metabolite by tissues is not unique to plasma acetate metabolism.…”