Page 33 - Academic Press Encyclopedia of Physical Science and Technology 3rd InOrganic Chemistry

P1: ZBU Final Pages
Encyclopedia of Physical Science and Technology EN002F-55 May 22, 2001 21:6

Bioinorganic Chemistry 121

Inresponsetocadmium,theplantcellcanrespondusing resents a significant environmental toxin. Arsenic is found
a number of defense systems. Some plants bind cadmium at dangerous concentrations in drinking water in areas
via histidine interactions to the cell wall. Cadmium that throughout southern Asia. As many as 15 million peo-
bypasses the cell wall then must pass the cell membrane. ple in that area suffer from arsenic poisoning. Arsenic
V
3−
This barrier at least slows the influx of cadmium into the is found in two forms, arsenate (As O ) and arsenite
4
III
−
cytoplasm. The cell membrane is usually breached by hi- (As O(OH) ). One mechanism of bacterial resistance to
2
jacking an ion channel meant for the influx of another ion. arsenic is mediated by genes on the ars operon. These
When cadmium enters the cell, the initial cell response is genes produce proteins that are responsible for the reduc-
to produce chelating agents, phytochelatins, to bind to the tionofarsenatetoarsenite,followedbyremovalofarsenite
cadmium rendering it ineffective. Phytochelatins are short through an ion pump.
peptides, typically 5–20 amino acids long, that are synthe- Other metals such as magnesium, silver, chromium,
sized from glutathione and contain repeating γ Glu–Cys nickel, manganese, zinc, and copper are all regulated by
units. different enzymes, but the general mechanism exhibits
A very significant mechanism of Cd detoxification is characteristics like those described above.
compartmentalization. By limiting the intracellular Cd to
vacuoles, the cytoplasmic Cd concentration is decreased
E. Regulation of Expression
and cadmium is effectively removed from the areas where
of Non-Inorganic Proteins
it can be toxic. After the cadmium is complexed to phy-
tochelatins, these complexes can associate with acid-labile Some regulatory proteins that contain inorganic ions reg-
2−
sulfur (S ) to form a higher molecular weight aggregate ulate the expression of proteins and enzymes not involved
with higher affinity toward Cd. This complex can then be with inorganic ion homeostasis. Unlike the proteins that
transported into a vacuole. Here the cadmium is tranferred have been mentioned before, zinc-containing transcription
from the phytochelatin to an organic salt (e.g., citrate, ox- factors do not regulate zinc homeostasis. Cells that are
alate, or malate) allowing the phytochelatin to return to zinc-starved are prone to growth problems because zinc
the cytoplasm to retrieve more cadmium. is an integral part of many transcription factors involved
For humans, recent data indicate adverse health effects in cell proliferation. In fact, humans deficient in zinc have
from cadmium exposure may develop in ∼1% of the adult hindered growth. The two most common motifs in zinc
population, and in high-risk groups this percentage will be transcription factors are the zinc finger and the Zn 2 Cys 6
even higher (up to 5%). Smokers have four to five times motif, typified by TFIIIA and GAL4, respectively.
higher blood cadmium concentrations and twice the kid- TFIIIA was the first zinc finger enzyme to be identified.
ney cortex concentrations as nonsmokers. In the human It contains nine zinc atoms, each stabilizing a region of the
body, cadmium is bound to albumin in blood plasma af- peptide known as a zinc finger. Zinc fingers are small re-
ter free cadmium ion has entered the blood stream. This gions of the protein (25–30 amino acids long) that fold
cadmium–albumin complex is recognized by the liver. into a distinctive α-helix–β-sheet conformation in pres-
Once in the liver, it is bound by a proteins called met- ence of Zn(II) (Fig. 2), allowing the α-helix portion of
allothionines (MT). Metallothioneins are small proteins, the structure to recognize DNA through major groove in-
4500–8000 Da, that contain a high proportion of cysteine teractions. Most zinc fingers contain two histidines and
residues (about 30%). These proteins chelate Cd much two cysteines responsible for binding the Zn(II) ion, al-
like the phytochelatins. Free cadmium induces synthesis though some are found with a Cys 3 –His zinc ligation. In
of MT, protecting the liver from cadmium toxicity. The fact, all nine zinc fingers in TFIIIA contain the consensus
Cd is returned to the blood stream complexed to MT and sequence (with minor variation) YXCX 2,4 CX 3 FX 5 LX 2
is transported to the kidney. There MT is degraded and HX 3,4 HX 2−6 . When these fingers are placehhd head-to-tail
free cadmium is released to react with sensitive sites or to in a protein, they are able to recognize specific sections
re-bind to albumin. Because of this loop, cadmium accu- of DNA. Since the discovery of zinc fingers in TFIIIA, a
mulates in the kidney and remains in humans a very long multitude of proteins have been discovered which contain
tong time (half-life is 10–15 years). Although plants have anywhere from 1 to 37 zinc finger motifs. Many of these
metallothionines, their role in the detoxification of heavy proteins are responsible for DNA recognition.
metals from plants has yet to be investigated. Another family of zinc transcription factors is exempli-
fied by GAL4. GAL4 is responsible for the transcription
of genes involved in galactose metabolism in yeast cells.
D. Regulation of Other Inorganic Ions
When zinc was initially discovered as a necessary con-
While many Americans learn of arsenic poisoning from stituent in GAL4, the protein was thought to contain a
the classic play “Arsenic and Old Lace,” this element rep- zinc finger with four ligating cysteines. Further studies