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Encyclopedia of Physical Science and Technology EN002F-55 May 22, 2001 21:6

Bioinorganic Chemistry 123

brane. Calcium is then released and more calcium is bound
on the other side of the membrane. This calcium again fa-
cilitates binding and hydrolysis of ATP, resulting in trans-
port across the membrane. This cycle continues until the
calcium concentration is sufficiently low enough to cause
calmodulin to release it. The calmodulin then releases the
ATPase and efflux of calcium stops.

II. INORGANIC COMPONENTS
OF ENZYMATIC SYSTEMS

A. Overview

FIGURE 3 Schematic of mediated transport: active and passive Perhaps the classic area of bioinorganic chemistry is the
ion transport. study of enzymatic systems that use inorganic atoms to
charry out catalysis. These studies have been undertaken
by looking at the enzymes themselves or by examining
be classified into two categories, passive-mediated trans- small molecules that have structural elements found at
port and active-mediated transport (Fig. 3). Passive medi- the active site of the enzyme. This small-molecule mod-
ated transport simply increases the rate of concentration eling approach has provided an invaluable source of data
equilibration between the two sides of a membrane. Ac- for understanding the electronic structure and chemical
tive transport moves ions from areas of low concentration mechanism of many complex enzymes. In some respects,
to areas of higher concentration, thus against a potential bioinorganic chemistry includes all enzymes because sol-
gradient. To overcome this gradient, active transport must
uble enzymes are dissolved in a sea of salt water con-
be coupled to an energy-utilizing reaction, usually the hy-
taining sodium, potassium, and calcium ions that perform
drolysis of ATP.
some level of perturbation on the structure and/or reac-
Valinomycin is a cyclical molecule that passively me-
tivity of the enzyme. However, this subsection of bioinor-
diates transport of K across membranes in the presence
+
ganic chemistry is usually limited to those enzymes that
+
+
+
of Na and Li . Valinomycin binds K octahedrally and bind a specific inorganic cofactor in a specific manner and
encompasses the ion in a shell that is very soluble in use it to perform a specific task.
the lipophilic membrane. After passing through the mem- The binding of the metal to the enzyme usually occurs
brane, potassium is released on the opposite side. Valino- through a set of amino acid ligands. Some amino acid lig-
mycin forms a relatively large binding pocket that leads to ands and the ways they bind to metals are shown in Fig. 4.
ion selectivity. Sodium and lithium ions are significantly Although this is the most common method of positioning
smaller than the pocket; they do not bind to valinomycin as the metal, some enzymes have evolved hydrogen bonding
efficiently and do not result in the structural change that schemes to freeze a solvated inorganic ion in a particu-
increases valinomycin diffusion through the membrane. lar location. Other enzymes will use an exogenous (non
Monensin is a similar molecule with a smaller binding amino acid) ligand to help stabilize the metal in the posi-
pocket, and transfers sodium ions across membranes in a tion desired. Still other enzymes use a combination of two
similar fashion. or more of these modes of binding.
Active-mediated transport of Ca 2+ ions from the cy- Among the tasks assigned to inorganic elements in en-
toplasm to the ER or excretion of Ca 2+ ions from a cell zymatic systems are stabilization of the protein structure,
is essential to retain the low concentration of Ca 2+ nec- transfer of electrons, transfer of oxygen, protection from
essary for cell signaling (described above). Removal of oxidative stress, activation of diatomic molecules such as
calcium from the cytoplasm is achieved through the use nitrogen, oxygen, and hydrogen, and harvesting light. Be-
ofaCa –ATPase that is regulated by Ca–calmodulin.
2+
low, a number of these enzymes are organized according
The Ca –ATPase contains a short polypeptide sequence
2+
to their task and described following a discussion on some
that blocks Ca 2+ binding to the ion channel in the absence
general inorganic structures used in these systems.
of Ca–calmodulin. In the presence of Ca–calmodulin, this
peptide changes its conformation and allows the binding
B. General Structures and Inorganic Cofactors
of calcium, which facilitates binding of ATP. When ATP
is hydrolyzed by the enzyme, the structure of the enzyme The metal centers found within enzymatic systems are
changes, introducing Ca 2+ to the other side of the mem- diverse. Among the “bioinorganic chips” are hemes,