Transcript INTRODUCTION to BIOENERGETICS H.R. Kaback

Inaugural lecture
H.R. Kaback
Bioenergetics in energy-transducing
membranes represents the bridge between
biochemistry and physiology. While ATP is the
currency of energy exchange in the cytosol,
electrochemical ion gradients across energytransducing membranes are involved in a large
number of seemingly unrelated processes such
as oxidative phosphorylation, active transport of
many different metabolites, signal transduction,
maintenance of internal pH, intracellular
organelle function, protein secretion, bacterial
motility, and other cellular processes.
Epithelial transport.
Transport across the epithelium of the intestine will be
discussed briefly merely to demonstrate the similarity
of the basic principles. The topic will be discussed in
more detail by Professor Wright. At the lumenal or
brush-border side of this polarized intestinal epithelial
cell (top), sodium and glucose are symported via a
sodium-coupled symport protein (SGLT1), leading to
accumulation of glucose against a large concentration
gradient in the cytosol. The accumulated glucose is
then allowed to flow down its chemical gradient via a
glucose uniporter (a.k.a., facilitated diffusion carrier) on
the basolateral surface (bottom) into the serosal fluid,
and sodium is pumped out on the basolateral surface
by the Na+/K+-ATPase. The tight junctions keep the
membrane proteins on the brush border from mixing
with the proteins on the basolateral membrane and vice
versa.
Synaptic function in the CNS.
At neuromuscular junction, acetylcholine is
released from pre-synaptic cells and binds to the
nicotinic acetylcholine receptor on the muscle cell
membrane, thereby opening a sodium channel
which leads to depolarization of the post-synaptic
muscle cell. Subsequently, the signal is terminated
by acetylcholine esterase which hydrolyzes the
neurotransmitter, and in addition, the acetylcholine
receptor becomes desensitized. In contrast, at
synapses in the CNS, the primary means of
terminating the signal is by re-uptake of
neurotransmitters (e.g., dopamine, serotonin,
glutamate, glycine) into the pre-synaptic cell and
subsequent repackaging into synaptic vesicles.
The next three lectures* will focus primarily upon one
aspect of bioenergetics, active transport of metabolites
in a specific experimental model system, bacterial
cytoplasmic membrane vesicles, which revolutionized
the field by leading to the development of similar
systems from epithelia and the nervous system. The
intent is to use this highly defined system to give you a
feel for what an electrochemical ion gradient is, how
the components are measured in microscopic systems
that are not readily amenable to electrophysiology and
how one can demonstrate convincingly that an
electrochemical ion gradient is the immediate driving
force for the accumulation of metabolites. The general
relevance of this relatively simple experimental system
to more complex systems that have direct relevance to
human physiology will be illustrated.
Reading:
Lectures from Professors Bezanilla and Wright
contain related information that will help you
understand the concepts under consideration.
For those of you who would like more in-depth
reading, the following are suggested:
Kaback, H.R. 1971. Bacterial membranes. Methods
in Enzymology 22, 99-130; Nichols, D. G. and
Ferguson, S. 1992. Bioenergetics 2 (Academic
Press, London).