2. Nitrogen fixation
Nitrogen is converted of N2 to N compounds.
Blue-green algae are some of the bacteria which are able to fix nitrogen.
Nitrogenase was isolated from anarobic bacterium colstridium pasteranium in 1960.
Nitrogenase is found to have two compounds Mo-fe containing protein and Fe containing
protein.
The Mo-Fe protein contains two Mo and about 30 atoms each of Fe and sulfide per
molecule.
The Fe protein contains two identical sub-units each containing Fe,S cluster.
3. Nitrogenase reduces N2 to NH3
N2 +8H+ +16Mg ATP + 8e → 2NH3 + H2+16Mg ADP +
16P04 -3
The ammonia produced is consumed for cell growth. The
electrons required are obtained by reduced forms of
ferredoxin and flavodoxin.
ATP is essential for nitrogenous activity.When the Fe-Mo
protein accumulates enough electrons (8 per N2) these are
transferred to N2 with proton transfer from water
4. The reduction of dinitrogen occurs at the Mo site of the
enzyme.
The ultimate source of reductive capacity is pyruvate,
and the electrons are transferred via ferredoxin to
nitrogenase.
There is some evidence, the Mo(III) is involved. Two
Mo(III) atoms cycling through Mo(VI) would provide six
electrons necessary for reduction of N2
5. Metal ion transport and storage
Ionophores
Some naturally occurring molecules have the ability to encapsulate a metal ion from several coordination sites and
at the same time provide a layer of organic groups outside the complex.
Valinomycin and nonactin are such cyclic proteins. These compounds resemble crown ethers and cryptates.
Valinomycin, a 36 membered flexible macrocycle can adopt various geometries depending upon the polarity of
surrounding medium and the presence or absence of a metal ion within its cavity.
The different conformations are stabilized by H-bonds between different parts of the molecule or to the solvent
6. It forms a 1:1 complex with K+, which fits nicely into the
cavity with the 6 carbonyl O-atoms pointing inward in an
approximately octahedral coordination around the metal.
The K complex is nearly 1000 times stronger than that
made by the Nation, which is only loosely held within the
cavity.
7. Nonactin is another naturally occurring ionophore. In the
metal free crystalline form, the carbonyl oxygens point
outward and the four oxygens from the four
tetrahydrofuran rings form nearly a square at the center.
On coordination to an alkali metal ion, the conformation
changes to form a nearly cubic arrangement of four
carbonyl O and four ether O around the cation providing
an extremely nonpolar periphery.
8. Transferrin
Transferrin is a protein that binds Fe(lll very strongly and transport it from the stomach into bloodstream.
Transferrin protein transport iron to the ferritin.
Humans and other animals absorb iron as Fe(II) from food in their digestive systems. As Fell) passes from the
stomach (which is acidic) into the blood (pH=7.4), it is oxidized to Fe() in a process catalized by the Cu
metalloenzyme ceruloplasmin.
Then binds with transferrin protein and transported to bone marrow where it is released and stored as ferritin.
Fe ion is then used to synthesis the other iron compounds such as hemoglobin,myoglobin and cytochromes
9. Transferrin is a single-chain polypeptide with a molar mass of 76,000- 80,000
There are two Fe(III) binding sites
These Fe binding proteins are responsible for the transport of Fe to the site of synthesis of other
iron-containing compounds (such as haemoglobin and cytochromes) and its insertion via
enzymes into the porphyrin ring.
The iron is present in the +3 oxidation state and is coordinated to 2 or 3 tyrosy residues, a couple
of histidyl residues. Tyrosine is providing a phenolic oxygen for coordination
10. The Fe is bound only if a suitable anion also is bound.
Several anions can promote the binding of Fe, but
carbonate (or HCO3-) is the physiologically active one.
The Fe is transported to bone marrow by transferrin
which can specifically recognize reticulocytes (immature
red blood cells) Since Fe used each day in building red
cells in an adult is about 10 times the amount of Fe
bound in transferrin, many cycles are required during the
lifetime of a protein molecule.
11. Ferritin
It is one of the principal iron storage compounds in human body.
Red-brown water soluble ferritin consists of a shell of protein (called apoferritin),surrounding a micelle of
iron(III) hydroxide phosphate.
The micelle (an aggregate whose surface bears a charge) contains about 2000 4000 Fe atoms.
The apoferritin shell has 24 subunits consisting of coiled polypeptide chains, each of molar mass about
18,500
Ferritin stores Fe(III) in spleen, liver, and bone marrow.
Ferritin releases iron by reduction to Fe(II) or by chelating agents
12. Medical applications
Cis-diamminedichloroplatinum(II) is an anticancer drug.
Cisplatin is administered as i.v. injection every few weeks- solutions are usually given in saline (NaCl). Kidney
toxicity, nausea, vomiting and drug resistance are some of the side effects of the drug.
The mode of action of cisplatin rests on its capacity to bind to DNA and block replication.
The Pt binds to DNA, with the chloride ligands first being replaced by water molecules and then by a DNA base
such as guanine.
The Pt(il) binds to two nitrogen (N-7) atoms of two adjacent guanine bases-mostly in the same strand to form a
chelated intrastrand cross-link.
13. The cross linking sharply changes the angle between the planes of the base molecules which were formerly parallel
The axis of the helix kinks by an angle ranging from 40-70°. This kink essentially sterically prevents replication of the DNA and thus
inhibits growth of the tumour cells.
In DNA replication, the H bonds linking the two strands of a DNA molecule break apart; each strand now collects nucleotides from the
nucleus to synthesize a complementary strand.
This produces two daughter molecules, each identical to the mother DNA.During transcription, The DNA acts as a template for the
synthesis of messenger RNA which carries the genetic code.
Cisplatin disturbs all these processes by blocking a strand in the DNA
