Page 34 - Academic Press Encyclopedia of Physical Science and Technology 3rd InOrganic Chemistry

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122 Bioinorganic Chemistry

if a hormone binds to a receptor that releases ATP on the
other side of a membrane, the hormone is considered the
first messenger, while the ATP is a second messenger).
Calcium is one of the most extensively used messengers
in biological systems. It is used in the signaling processes
of muscle contraction, secretion, protein degradation, and
cell division. For a long time, calcium was considered a
second messenger. Evidence, however, suggested that the
major source of calcium used in signaling comes from the
endoplasmicreticulum(ER),whichresidesentirelywithin
the cell. This observation requires a second messenger to
transmit a signal from the outside of a cell through the
cytoplasm to the ER, making calcium the third messen-
ger. It was discovered that an organic molecule, inositol
triphosphate, acts as the second messenger.
One requirement of a messenger in processes such as
muscle contraction that require quick response time is that
it must be found in low concentrations in the absence of a
signal. This requirement is satisfied for calcium. Although
the concentration of calcium in sea water, human plasma,
and the ER is about 10 mM, the concentration of calcium
within the cytoplasm is 0.0001 mM. This difference pro-
vides very dramatic changes in the calcium concentration
upon leakage of calcium into the cytoplasm from the ER.
This gradient, however, requires very efficient ion chan-
nels for calcium (discussed in the next section).
After calcium is released from the ER, one way it trans-
mits the signal to the target protein is through calmod-
ulin. Calmodulin is a protein that can bind four Ca 2+ ions.
The binding of calcium induces a structural change that
exposes a methionine-rich region of the protein. Calmod-
ulin then binds to proteins containing a site, a calmodulin-
FIGURE 2 Section of transcription factor IIIa bound to DNA: an binding domain, that recognizes this methionine-rich re-
example of zinc finger binding.
gion. This interaction can cause structural change in the
target protein that regulates its activity. An example of
a calmodulin-regulated protein is nitric oxide synthase
revealed the presence of the binuclear Zn 2 (Cys) 6 ligation (NOS). NOS produces nitric oxide, NO, which is a mes-
geometry. Similar to the zinc in zinc fingers, the dimeric senger involved in vasodilation and inflammatory re-
zinc site in GAL4 stabilizes the DNA-binding domain. sponse. Calmodulin also activates the ATPase that pro-
vides the energy to pump calcium out of the cell against a
potential gradient.
F. Cell Signaling
For a cell to function, it must be able to transmit signals G. Ion Channels
from one compartment of a cell to another. This usually
+
2+
requires transmitting a signal through a cell membrane. To ingest and excrete ions (such as Na ,K ,Ca , and
+
This mechanism is usually accomplished through a se- Cl ) from and to the surrounding environment, cells must
−
ries of receptors and messengers. Receptors are enzymes pass these ions through a membrane. In addition, eukary-
that receive the signal from one side of a membrane and otic cells are compartmentalized by intracellular mem-
transmit it to the other side. Messengers transmit the sig- branes that must also be traversed by these ions. There are
nal between receptors and ultimately to the proteins that two types of transport across the cell membranes: medi-
are induced by the signal. Messengers range in size from ated and unmediated. Unmediated transport is via simple
small molecules and ions to proteins, and are labeled ac- diffusion, whereas mediated transport occurs through the
cording to the order in which they occur in the signal (e.g., action of specific carriers. Mediated transport can further