TRANSITION METAL IONS

IN BIOLOGICAL SYSTEMS
 INTRODUCTION
• Atoms that make up the human body
• 70 % - water
• 29 % - C, H, N, O
• 0.9 % - Na, K, Ca, Mg, P, S and Cl
• 0.1 % - trace elements :
– 9 transition metals: V, Cr, Mn, Fe, Co, Ni, Cu,
Zn and Mo: are natural constituents of
protein = metalloproteins
 The metallic elements play a variety of roles in
biochemistry.

The ability of metal ions to

• coordinate and release ligands in some
processes,
• oxidize and reduce
• form complexes with a type of macrocylic
ligand called a porphyrin.
 metalloproteins
Play 3 essential roles in biochemistry
Act as transport and storage agents:
 Moving small molecules from place to place within an
organism
Are enzymes
 Catalysts for a diverse group of biochemical reactions
[both transport and catalysis depend on the ability of
transition metals to bind and release ligands]
To serve as redox reagents
 Adding and removing electrons in many different
reactions
[ability of transition metals to cycle between 2 or more
oxidation states]
 macrocyclic ligand : A metal ion is surrounded by the
four nitrogens of a phophine ring in a square-planar
geometry and the axial sites are available for other
ligands.
 TYPES OF PORPHYRINS

Different side chains, metal ions, and surrounding

species result in very different reactions and roles
for these compounds. For example, metal ions are
present in:
 Hemoglobin : iron ion Fe2+
 Chlorophylls: Magnesium ion Mg2+
 Enzymes: Cytochromes; P-450: iron ion Fe2+
 Vitamin B12: Coenzyme B12: cobalt iron Co2+
 Heme
• Heme-unit is part of Hemoglobin, Myoglobin,
Cytochromes and several enzymes. They differ by
the proteins surrounding the heme.
 hemoglobin
• consists of a tetradentate ligand, heme, combined
with a protein (globin) which together coordinate
with an iron atom in five positions.
• The sixth position in the octahedrally-coordinated
iron is taken up either by an oxygen molecule or by a
water molecule, depending on whether the
hemoglobin is in its oxygenated state (in arteries) or
deoxygenated state (in veins.)
In hemoglobin and myoglobin: the fifth coordination site of the iron is
occupied by the nitrogen of a histidine, which is part of a protein. The
sixth coordination site can reversibly bind oxygen.

Hemoglobin transports oxygen from the lungs to the cells of the

body and there it transfers the oxygen to myoglobin which
contains only one heme unit (Hemoglobin: 4 heme unit) The
myoglobin makes the oxygen available to the respiratory reactions
of the cell.
 Hemoglobin exists in two forms
• Depending on the nature of the sixth ligand
• in the blood vessels of lungs, high [O2], heme binds
O2 to form oxyhemoglobin, transported in the
arteries to O2-depleted tissues
• At these tissues, O2 is released and replaced by H2O
to form deoxyhemoglobin, transported in the veins
back to the lungs
 Transport and storage metalloproteins

• Organisms extract energy from food by using molecular

oxygen to oxidise fats and carbohydrates
• For most animals, the movement and storage of O2 is
accomplished by the iron-containing proteins
haemoglobin and myoglobin
• Haemoglobin binds O2 = oxyhaemoglobin : transports
O2 from lungs to various parts of the body where
oxidation takes place.
• Myoglobin stores O2 in tissues (muscle)
 O2 vs H2O [Fe2+: 3d6]
• Oxyhemoglobin -O2 : strong
field ligand
– Increase the splitting
energy o
– Low-spin complex
– Absorbs at the blue (high
energy) end of the visible
spectrum
– Give bright red colour of
arterials blood
• Deoxyhemoglobin-H2O
Weak field ligand
– Decrease the splitting
energy o
– high-spin complex
– Absorbs at the red (low
energy) end of the visible
spectrum
– Give bright dark colour of
venous blood (Bluish)
– Silberberg pg-1035-1036
 Cooperative teamwork
• The position of Fe2+ relative to the phorphin plane
depends on the 6th ligand
• Fe2+-O2 : in the plane : normal octahedral
• Fe2+-H2O : move-out the plane ; distorted octahedral
• This tiny change influence the shape of globin chain,
triggering the release or attachment of O2
• Allows hemoglobin
to pick up O2 rapidly
from the lungs &
unloads it rapidly in
the tissues
 Hemoglobin : cooperative
• These changes nudge the neighboring chains into a
different shape, making them bind oxygen more easily.
• Thus, it is difficult to add the first oxygen molecule, but
binding the second, third and fourth oxygen molecules
gets progressively easier and easier.
• This provides a great advantage in hemoglobin
function.
OR:
Deoxyhemoglobin is relatively uninterested in oxygen, but
when one oxygen attaches, the second binds more easily,
and the third and fourth easier yet. The same process works
in reverse: once fully loaded hemoglobin lets go of one
oxygen, it lets go of the next more easily, and so forth. This
relationship -- called cooperativity
 Hemoglobin
• In this environment, hemoglobin releases its
bound oxygen. As soon as the first oxygen
molecule drops off, the protein starts changing
its shape.
• This prompts the remaining three oxygens to be
quickly released.
• In this way, hemoglobin picks up the largest
possible load of oxygen in the lungs, and
delivers all of it where and when needed.
 Hemoglobin : competitive inhibitor
(CO2, CO, CN…. )
• When blood is in the lungs, where oxygen is plentiful,
oxygen easily binds to the first subunit and then quickly
fills up the remaining ones.
• Then, as blood circulates through the body, the oxygen
level drops while that of carbon dioxide increases.

CO POISONING
 CO is “competitive inhibitor” of O2.
 Affinity is 200X greater than that of O2.
 CO also inhibits unloading O2 of in tissues.