BIOINORGANIC CHEMISTRY A Short Course Second Edition

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POTASSIUM-DEPENDENT MOLECULES 199

electrogenic system. The large membrane potential thus generated yields
hydrolysis energy of ATP — the free energy stored in the living cell. This energy
will be used for impulses (messages) sent by nerve cells, for exchange reactions
to accumulate or dissipate other chemicals (amino acids perhaps), for coupling
to other reactions such as oxidations or phosphylations, and for the synthesis
of new raw materials needed by the cell.
In summary, homeostasis for potassium, sodium, calcium, and chloride ions
must be controlled carefully so that current (life) is always fl owing. Critical
balances among these ions, as well as pH control, maintains the ionic charac-
teristics of physiological systems in (1) osmotic pressure balance, (2) electrical
potentials involving membranes, (3) interaction with polyelectrolytes (pro-
teins and DNA), and (4) connections to the uptake of organic metabolites. All
systems are linked through their energy requirements, normally stored in the
pyrophosphate of ATP. Figure 21.20 of reference 2 shows a schematic diagram
connecting extracellular levels of Na + , K + , Ca 2+ , and Cl − , ATP energy used by
ion pumps, Zn 2+ levels inside cells, Fe 2+ /Fe 3+ levels inside mitochondria, meta-
bolic pools, and hormones, and as the authors state: “ Protons are involved
everywhere. ”

5.4 POTASSIUM - DEPENDENT MOLECULES


This section will concentrate on requirements for potassium ions as cofactors
in biological molecules. In doing so, one involves another Group I metal
ion — sodium — in discussing the sodium pump, Na + /K + ATPase (Section 5.4.1 ).
Sodium ions are intimately involved in the activity of other biomolecules — the
voltage - gated sodium ion channels, for instance. We will not discuss the sodium
ion channels here, but will concentrate on potassium ion channels in Section
5.4.2. Voltage - gated potassium ion channels are implicated in genetic and
autoimmune diseases, making potassium ion channels therapeutic targets in
drug design research. The biological activity of the lithium ion rests mostly in
(a) its inhibitory effect on many enzymes and (b) its multiple effects on some
physiological processes. Lithium is highly effective in the treatment of bipolar
disorder, however, the mechanism of lithium action in the treatment of this
psychiatric disorder is still unknown. The Group I ion ’ s biological activity will
not be discussed further here.

5.4.1 Na+/K+ ATPase: The Sodium Pump,


The enzyme Na + /K + - ATPase is a highly conserved integral membrane protein
that is expressed in virtually all cells of higher organisms. Na + /K + - ATPase has
been estimated to hydrolyze nearly 25% of all cytoplasmic ATP in resting
humans. In nerve cells, approximately 70% of the ATP is consumed to fuel
this enzyme. More basic information about Na + /K + - ATPase can be found at
the website http://arbl.cvmbs.colostate.edu/hbooks/molecules/sodium_pump.
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