respiration inhibited by ouabain (and
hence assumed to represent Na+,K+-ATPase
activity) varied with both dietary treatment
and acetate concentration. Supplying addi-
tional UDP (at constant eRDP:FME)
lowered (P< 0.01) the proportion of total
respiration attributable to sodium pump
activity by a constant amount at each acetate
level whilst increasing acetate increased it
linearly such that the percentage inhibition
could be described by the following
equation: %inhibition = 16.6 + 4.05
acetate concentration (mM) (R^2 = 0.65,
P< 0.001). This represents a change in the
pattern of use of energy by liver tissue
since, as total respiration rate did not alter
as acetate level increased, so a greater
proportion of energy production had to be
diverted towards sodium pump activity.
From these results, it can be calculated
that for acetate to cause an increase in
sodium pump activity via the mechanism
shown in Fig. 7.2, the rate of efflux of
acetatewould have to be 4.3 nmol min^1
mg^1 protein, equivalent to a permeability
of 1 10 ^7 cm s^1. This value is very close
to those calculated for HCO 3 and NH 4 +
and is in good agreement with one report
of a measured permeability of the plasma
membrane to acetateof 3.4 10 ^7 cm s^1
(Sharp and Thomas, 1981; Hume and
Thomas, 1989). For efflux of acetate to
take place, there must be a suitable ‘driving
force’; this would be provided by the
substantial electrochemical gradient (posi-
tively charged on the extracellular surface
and negatively charged on the intracellular
one, thus repelling negatively charged ions
from the cell) that exists across the plasma
membrane (equivalent to a concentration
gradient of ~100 mMfor acetate).
Carbon dioxide is produced continually
within mitochondria from oxidative meta-
bolism. It diffuses down its concentration
gradient to the extracellular fluid. The
potential exists for hydration of CO 2 to
carbonic acid and then dissociation to H+
and HCO 3 . Many tissues possess the
enzyme catalase which greatly speeds up
attainment of this equilibrium. The pro-
duction of protons and bicarbonate from
CO 2 results in what is termed facilitated
diffusion of CO 2 from tissues (Gros et al.,
1988). The HCO 3 anion exchanges for Cl
across the plasma membrane and the H+is
pumped out of the cell by the Na+/H+
antiporter. In studies with muscle tissue,
where the rate of CO 2 production can
increase substantially during exercise, this
process of facilitated diffusion has been
estimated to account for 70% of CO 2
removal from the tissue (Gros et al., 1988).154 N.S. Jessop
Fig. 7.2.Representation of acetate cycling across the plasma membrane. AcH refers to acetic acid in its
undissociated form, Acthe acetate anion, membrane protein 1 is the Na+/H+antiporter and membrane
protein 2 is Na+,K+-ATPase.