Page 30 - Academic Press Encyclopedia of Physical Science and Technology 3rd InOrganic Chemistry

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

118 Bioinorganic Chemistry

essential role in biological systems, giving this area of sci- regulation, respectively. All three types of regulation are
ence the seemingly contradictory title. In fact, in most of employed to control the concentration and location of in-
the major functions of life—respiration, photosynthesis, organic ions in a cell. Furthermore, most inorganic ions
reproduction, oxygen transport, and metabolism, to name account for their own regulation. Metal-regulated gene
afew—inorganic ions play an active and essential role. expression can be considered to fall into three categories:
(1) maintaining homeostasis of an essential element such
as iron or copper, (2) removing or detoxifying elements
I. INORGANIC ION UPTAKE with no useful biological activity (e.g., mercury or cad-
AND REGULATION mium),and(3)controllingexpressionofgenesthatencode
proteins that may or may not use the specific element (e.g.,
A. Overview zinc fingers).

Microbes, plants, and animals must be able to generate
an organized structure from a surrounding disorganized B. Acquisition and Regulation of Iron
milieu. Table I compares the concentrations of several es- and Other Essential Elements
sential elements in sea water to levels found in human
Iron is one of the most abundant inorganic elements in
plasma. In most cases, the elements are more concen-
biology. Iron is essential in processes as diverse as photo-
trated in human plasma. This observation points to the
synthesis, respiration, and destruction of oxygen species
necessity of having an uptake mechanism for inorganic
that lead to damage in biomolecules. Iron can also be very
elements in humans. The same requirement is true for all
toxic. The deleterious side reactions of iron result in detri-
organisms. Not only do organisms need to acquire ele-
mental processes in humans such as aging, cancer, and car-
ments from the environment, they need a mechanism to
diovascular disease. A large excess of iron(III) deposits as
ensure that toxic concentrations are not attained. This in-
rust in a protein called hemosiderin, which accumulates in
terplay between uptake, storage, and excretion is termed
cell membranes. In thallesemia major, a genetic blood dis-
regulation. Homeostasis of these inorganic ions in cells
ease,hemosiderindepositsadverselyeffectcellmembrane
is accomplished by regulating the synthesis of the pro-
function. Even more pernicious, iron can react with oxy-
teins and small molecules that are involved in the uptake,
gen or peroxide to form the same oxygen radicals that it is
storage, and discharge of that particular inorganic ion.
used to prevent. Hydroxyl radical is produced from hydro-
A general scheme of inorganic ion regulation is shown
gen peroxide through a process called the Fenton reaction:
in Fig. 1. With the exception of retroviruses, all proteins
are encoded in DNA. DNA is transcribed to form RNA Fe 2+ + H 2 O 2 + H −→ Fe 3+ + H 2 O + OH. (1)
+
by RNA polymerase. RNA is then used to make proteins
in the ribosome. Proteins can then be modified to acquire Hydroxyl radical reacts with molecules such as DNA or
the proper activity. Regulation of the production of en- lipids at diffusion-controlled rates every time it collides
zymes can occur at any of these steps. Regulation of RNA with one, and is the cause of lesions to genetic material
polymerase, ribosome function, and protein function are or cell membranes. Superoxide and peroxynitrite are
called transcriptional, translational, and post-translational two additional reactive species that can be formed in the
presence of excess Fe(II) as follows:
TABLE I Concentrations of Selected Inorganic Ele- Fe(II) + O 2 −→ Fe(III) + O − (2)
2
ments in Sea Water and Human Plasma
−
−
O + NO −→ OONO. (3)
2
Sea water Human plasma
Inorganic concentration concentration In particular, peroxynitrite has been implicated as an
element (Molar) (Molar) important causative agent of inflammation, nerve damage,
and the severe secondary tissue damage following heart
Iron 5 × 10 −11 to 2 × 10 −8 2.2 × 10 −5 attacks and strokes.
Zinc 8 × 10 −8 1.7 × 10 −5 Because iron concentrations must be tightly regulated,
Copper 1 × 10 −8 1.6 × 10 −5
organisms from archaebacteria to humans have developed
Molybdenum 1 × 10 −7 1.0 × 10 −5
complex processes to acquire iron from the environment,
Cobalt 7 × 10 −9 2.5 × 10 −11
transport it through the cell membrane, and insert it into
Chromium 4 × 10 −9 5.5 × 10 −8
the appropriate enzyme without being released to diffuse
Vanadium 4 × 10 −8 1.8 × 10 −7
freely where it can cause extensive damage to the cell.
Manganese 7 × 10 −9 1.1 × 10 −7
Given below are two examples of the regulation of iron,
Nickel 5 × 10 −9 4.4 × 10 −8
one from a prokaryotic organism, the other from humans.