MEDIATION OF HEXOSE TRANSPORT BY THE LIVER CELL MEMBRANE
MEDIATION OF HEXOSE TRANSPORT BY THE LIVER CELL MEMBRANE
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Date
1980-04
Authors
IBU, JOHN ODO
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Abstract
1. Transport of D-glucose, D-galactose and D-fructose across the
liver cell membrane was studied using an in situ rat isolated liver
perfusion technique.
2. A bench-top liver perfusion apparatus which maintains the liver
temperature constant for several hours of perfusion is described. This
apparatus has the advantages that it is simple, cheap, and effective.
3. The perfusion medium used was Krebs bicarbonate buffer to which
were added washed bovine erythrocytes and bovine albumin. This medium
was found to meet the requirements for a viable liver perfusion.
4. Stringent viability criteria were adopted and livers which failed
these criteria were rejected. Electron microscopic studies of perfused
and unperfused livers were undertaken as adjunct to viability assessment
of these livers.
5. The suitability of radioactively labelled sucrose as an extracellular
reference material in a double indicator dilution technique
in the perfused rat liver was investigated.
6. The hepatocellular transport of each of D-glucose, D-galactose
and D-fructose was saturable.
All the three hexoses showed mutual competition.
The single pass extraction values for the hexoses were consistently
different such that D-glucose>>D-galactose»D-fructose»»L-glucose.
7. D-glucose transport is by far greater than L-glucose transport
suggesting stereospecificity of glucose transport mechanism, confirming
the finding of the only previous study (WILLIAMS et al, 1968).
8. Both phlorizin and phloretin inhibited uptake of these hexoses.
Of these two phloretin was by far the better inhibitor, a finding
suggesting that the hepatic uptake of these sugars is analogous to
known passive (e.g. human erythrocyte) rather than active (e.g.
e.nterocyte) types of hexose transport.
9. Some dissaccharides were found to inhibit the uptake of these
hexoses. Lactose inhibited the uptake of all three hexoses. Maltose
inhibited uptake on D-glucose and D-fructose only (it had no effect
on D-galactose uptake). Sucrose had no effect on any of the three
hexoses.
10. Galactose transport was found to be temperature dependent. On an
Arrhenius plot there was a discontinuity of this temperature dependence
suggesting a transition temperature of about 31 C. A relatively
high activation energy (67 Kj mole at 37°C) was calculated from these
findings.
11. It was concluded, on the basis of the findings of saturability,
competition, stereospecificity and greater chemical inhibition of
hexose transport by phloretin than phlorizin, that these hexoses are
transported across the liver cell membrane by a facilitated diffusion
(carrier mediated) transport mechanism similar to that existing in
human erythrocytes. On the basis of dissacharide effects, it was
inferred that the D-galactose carrier mechanism is distinct at the
external surface of the membrane from the D-glucose/fructose carrier
mechanism. This implies an asymmetry between the external and internal
carrier sites, the latter probably being common to all three hexoses
whereas the former is distinct. An architecture for these carrier
sites in the liver cell membrane is proposed
Description
DEPARTMENT OF PHYSIOLOGY AND PHARMACOLOGY,
UNIVERSITY HOSPITAL AND MEDICAL SCHOOL,
NOTTINGHAM, ENGLAND,
.
BEING
THESIS SUBMITTED TO THE UNIVERSITY OF NOTTINGHAM
FOR THE DEGREE OF DOCTOR OF PHILOSOPHY.
APRIL 1980
Keywords
MEDIATION,, HEXOSE TRANSPORT,, LIVER CELL,, MEMBRANE.