METAL IONS IN BIOLOGICAL SYSTEMS

Dr. Rajeev Singh

(http://people.du.ac.in/~rajeev/index.htm)

Earlier it was thought, the chemistry involved in living organism is organic chemistry.
But gradually it was also found that metal ions also play key role in biological processes.

More than 52% of proteins characterized today contain metal ions. Requirement of
metal ion in biological processes is very specific. Specific metal ions in specific oxidation
states perform specific functions for example Hb contains Fe in +2 OS carries O2 while in +3
OS doesn’t carry it.

Bioinorganic chemistry

Bioinorganic chemistry is a field that examines the role of metals in biology. Bioinorganic
chemistry includes the study of both natural phenomena such as the behavior of metallo-
proteins as well artificially introduced metals, including those that are non-essential, in medicine
and toxicology. Many biological processes such as respiration depend upon molecules that fall
within the realm of inorganic chemistry. The discipline also includes the study of inorganic
models or mimics that imitate the behavior or metalloproteins.

Geochemical effect on the distribution of metal ions

All the most essential elements are fairly abundant in the earth crust except four: Al, Ti, Zr, Si
because of two reasons:

1. At biological pH value, they form insoluble oxides.

2. They don’t form reasonable stable complexes with biological complexing agents like amino
acids and proteins which are complexing agents in biological systems.

Well known toxic elements:

Pb: 1.3 x 10-3 %

Cd: 2 x 10-5 %
Hg: 5 x 10-5 %

These toxic elements are extremely rare in abundance in the earth crust. The life evolved
utilizing only those elements which were readily available and became dependent on them.
CLASSIFICATION OF ELEMENTS ACCORDING TO THEIR ROLE IN
BIOLOGICAL SYSTEMS

ESSENTIAL ELEMENTS: O C H N P Na K Mg etc: which are absolutely necessary for life

processes

TRACE ELEMENTS: Fe Zn Cu Mn Mo etc: They are also necessary for life processes but
these are present in biological systems in trace amounts.

NON ESSENTIAL ELEMENTS: Ba Sn Sr etc: They may be present in bio-system but they are
not necessary/ essential.

TOXIC ELEMENTS: Pb, Cd, Hg etc: They disturb the natural functioning of biological
processes.
Trace elements:

IRON, Fe

Deficiency: anemia because less iron means RBC contains less Hb, thus carry less amount of the
O2.

Excess: vomiting, shocks, circulatory collapse, coma.

Chronic condition: SIDIROSIS, iron gets deposited in tissues and organs.

Copper, Cu

Excess: WILSON’S diseases (0.11 g)

Highest concentration of Cu is present in the brain, kidney and liver. In Wilson,s disease, this
concentration goes upto 100 times and this results in neurological problems, kidney failure and if
condition is not treated then death.

Deficiency: mostly in infants, concentration of Cu containing enzymes (amine oxidase,

cytochrome C-oxidase) decreases.

TOXIC METAL IONS

The overall mechanism of toxicity is quite complicated but one can give three reasons for
toxicity of metal ions:

1. Blocking of essential biological functional groups.

2. Displacement of essential metal ions in biomolecules.
3. Modifying the active conformation of biomolecules

Explanation:
1. There are some essential biological functional groups – SH – M. Metal ion which cause
toxicity can bind with this group and block their functions.
2. Enzymes like carbonic anhydrase and carboxypeptidase contain Zn and if Zn is displaced
by toxic elements, the whole role of the enzyme is changed.
3. When a toxic metal is attached to protein or DNA or RNA, it will bind that and pull.
DNA is having active conformation (helical conformation) if that helical conformation is
lost, activity of biomolecule is lost.
MERCURY, Hg
Sources of toxicity:
1. Industrial waste (Minamata disease, minamata company released vinyl chloride, sea fish
affected)
2. Pesticides (chlor alkali industry uses Hg in formation of sodium hydroxide)
3. Mining
4. Coal and lignite

Reason for toxicity of Hg:

Hg bind strongly with SH (thiol) group of proteins and enzymes. Even the formation constant
between Hg-SH is 1016 – 1022 is very high.

RSH: mercaptants/ thiols: mercury capturing agents

There is strong soft-soft interactions between Hg and SH. It blocks activity of SH group of
proteins and enzymes and because of this strong binding it pulls that molecule and because of
that pull active conformation of molecule is modified and modification causes toxicity.

CADMIUM, Cd

Symptoms: nausea, salivation, vomiting, diarrhea, abdominal pain, brittleness of bones.

Chronic conditions: Cd deposits in kidney

Sources of Cd pollution: Metallurgical plants, Cd plating, Battery fabricators

Disease: Itai-Itai (ouch-ouch) occurred in japan in 1961

Reason for Cd toxicity:

Blocks the activity of functional groups mainly the SH group of enzymes or proteins because of
soft-soft interactions and lost the activity of this functional group. It modifies active
conformation of biomolecules.

LEAD, Pb

Largest user is battery industry but the source of pollution is due to gasoline exhaust.

Gasoline contains tetraethyl lead which is a anti knocking agent. As such this is not harmful, this
is converted to (C2H5)3Pb+: triethyl lead cation. This cation can cross the biomembrane and can
cause toxicity

Pb poisoning causes anemia. Pb can bind with SH group of enzymes or proteins. There is an
enzyme called ferrocholatase containing – SH.