| dc.description.abstract | INTRODUCTION
The purpose of this project was to investigate
the regulation of pathways of glutamate metabolism
in isolated rat - liver mitochondria. Special
emphasis was laid on the role of the two transport
systems for glutamate In the inner - mitochondrial
membrane namely:
1. + the glutamate - H symport system (alternatively
,described as glutamate - hydroxyl exchange diffusion
carrier) which is linked to the deamination pathway
of glutamate oxidation, leading to the formation
of ammonia and
2. the electrogenic exchRnge of extramitochondrial
glutamate (plus H+) for intramitochondrial
aspartate which is linked to the transamination
pathway of glutamate Qxidation, leading to the
formation of aspartate (plus CO2),
PART ONE
Glutamate Metabolism
A detailed study of the rate of formation of ammonla
and aspartate from added glutamate under different
metabolic conditions was done in order to confirm and
extend the work of other investigators (Borst, 1962;
De Haan, 1967). Effects of uncouplers, malate, Vitamin
K3, inhibitors of transamination pathway (arsenite,
malonate and aminooxyacetate) and inhibitor of
glutamate dehydrogenase (glutarate) were investigated
on the rate of formation of products of glutamate
oxidation. The effect of different inhibitors of the
+ glutamate - H translocator (avenaciolide, bromocresolpurple
and HEM) on the rate of glutamate oxidation
was studied under different metabolic conditions, particularly
in partially or fully uncoupled mitochondria
or in the presence of vitamin K3. These experiments
led to the following conclusions:
1. under many metabolic conditions the rate of
ammonia formation from added glutamate (and
thus presumably the rate of glutamate uptake V1a
the glutamate - H+ translocator) 1S far in excess
of the reported maximal activity of the glutamate -
H+ translocator (Meyer and Vignais, 1973;
Bradford and McGivan, 1973).
2. Except when the rate of ammonia formation was
maximally stimulated~ the inhibitors of glutamate
+ - H symport system did not have any inhibitory
- effect (unless very high concentrations were used)
indicating that the capacity of the transport
system exceeded the rate of glutamate oxidation.
Further information was obtained from studies on
the metabolism of intramitochondrially synthesized glutamate. from two systems. | en |
