Natural oxygen carriers

1. METAL COMPLEXES AS OXYGEN
CARRIERS: HEMOGLOBIN AND
MYOGLOBIN
VARINDER KHEPAR
PhD CHEMISTRY 1

2. INTRODUCTION
• Most of organisms require molecular oxygen for their survival.
• For some small animals and plants, where the surface-to-
volume ratio is large, the supply of dioxygen can be obtained
by simple diffusion across cell membranes i.e. extracted from
air or water or photosynthesis.
• For other organisms, from scorpions to whales, diffusion does
not supply sufficient dioxygen for respiration.
• In these organisms specialized molecules for the transport
and storage of oxygen are necessary.
• These functions are carried out by a number of well-known
iron and copper containing species which occur in the blood.
These are listed in table.
2

3. 3

4. METALLOPORPHYRINS
• Porphyrins are a group of hetero macrocycle organic
compounds, composed of four modified pyrrole subunits
interconnected at their α carbon atoms via methine bridges
(=CH−).
• Porphyrins are the conjugate acids of ligands that
bind metals to form complexes. The metal ion usually has a
charge of 2+ or 3+
• They act as tetradentate ligands with 4 N donor sites.
• The complexes in which a dipositive metal ion is held in the
porphyrin ring system are called metalloporphyrins
• Size of centre hole of ring is 0.201nm radius.
4

5. 5

6. MYOGLOBIN
• Was the first protein whose complete
tertiary structure was determined by X-
tray crystallography.
• Has 8 α-helical region and no β-pleated.
• Hydrogen binding stabilize the α-helical
region.
• Consist of a single polypeptide chain
includes prosthetic group- one heme
group.
6

7. • Myoglobin is a relatively small protein of molecular weight
of about 17000.
• It consists of one polypeptide chain (globin) with one heme
group (iron porphyrin complex ) embedded their in.
• The peptide chain consists of 150-160 amino acid residues
folded about the single heme group.
• The heterocyclic ring system of heme is porphyrin
derivative containing four pyrrole groups joined by
methylene bridges.
• The Fe2+ atom present at the centre of the heme is bonded
by four porphyrin nitrogen atoms and one nitrogen atom
from imidazole side chain of histidine residue which is a
part of long protein chain of amino acid residues.
• This polypeptide chain plays an important role in biological
fixation of O2.
7

8. (a) 3-D structure of myoglobin of whale (Physeter catodon) and (b)
Structure of the active site of myoglobin
8

9. Hemoglobin
haem
Prosthetic
group
globin
protein
9

10. 10

11. HEMOGLOBIN
• Hemoglobin is a larger protein
with a molecular weight of about
64500.
• It consists of four sub units each
of which contains one heme
group associated with protein
globin.
• There are four heme groups
bonded to four protein chains.
• One heme group with its protein
chain is called sub unit.
11

12. • Two sub units form alpha chains of 141 amino acids
and two form beta chains of 146 amino acids.
• The chains are coiled to form three dimensional
structures (also called tertiary structures) are quite
similar.
• The chain interact with each other through
noncovalent interaction – electrostatic interaction,
hydrogen bonds, and hydrophobic interaction
• Any changes in structure of protein- will cause drastic
changes to its property, this condition is called
allostery.
12

13. ALTERATIONS IN STRUCTURE OF
HEMOGLOBIN, LEADING TO DISORDERED
FUNCTION OF HEMOGLOBIN
REPLACEMENT OF ONE AMINO ACID IN
HEMOGLOBIN STRUCTURE LEADS TO
DISEASE!
Sickle cell anemia – molecular disease of hemoglobin
First case described in
1904 – J. Herrick,
Chicago physician
13

14. 14

15. BASIC FUNCTIONS OF HEMOGLOBIN
AND MYOGLOBIN
• Hemoglobin picks up oxygen in the lungs and
delivers it to the rest of the body.
• Myoglobin accepts oxygen from the
hemoglobin in the muscles and stores it until
needed for energetic processes.
• Deoxygenated hemoglobin uses some of its
amino groups to CO2 back to the lungs.
15

16. OXYMYOGLOBIN AND OXYHEMOGLOBIN
• As Hb and Mb have five coordinated Fe (II) atom.
• It is bonded by four nitrogen atoms from pyrrole rings and
fifth from protein chain.
• In these complexes, the sixth position is occupied by weakly
bonded water.
• Mb and Hb in such molecules are usually called as
deoxymyoglobin (deoxy-Mb) and deoxyhemoglobin (deoxy-
Hb).
• When molecular oxygen occupies the sixth position which is
trans to histidine chain, then these molecules are called
oxymyoglobin (oxy-Mb) and oxyhemoglobin (oxy-Hb).
16

17. Illustration of structural changes occurring in myoglobin after
oxygen is bound to it
17

18. 18

19. 19

20. 20

21. NATURE OF HEME-OXYGEN BINDING
• The dioxygen molecule (O2) can bind to iron in
heme group in the following three probable
ways:
• Linear arrangement
• Angular or bent arrangement
• Sideway symmetrical interaction
Fe O
O
Fe O O
Fe
O
O
21

22. OXYGEN TRANSPORT MECHANISM
• Hemoglobin and myoglobin play very
important role in transporting oxygen from
lungs to tissues and CO2 (as HCO-
3 ) from
tissues to the lungs.
• Oxygen is inhaled into the lungs at very high
pressure where it binds Hb in the blood
forming HbO2.
• The oxygen is then transported to respiring
tissues where the partial pressure of O2 is low.
22

23. • The O2 then dissociates from Hb and diffuses
to the tissues where myoglobin picks it up and
stores until it is needed.
• Mb has greater affinity for O2 than Hb. This
increases the rate of diffusion of O2 from the
capillaries to the tissues by increasing its
solubility.
• The Hb and CO2 (as HCO3
-) are then returned
to the lungs where CO2 is exhaled.
23

24. COOPERATIVITY
• COOPERATIVITY enables the Hb to bind and release oxygen more
effectively.
• When a substrate binds to one enzymatic subunit, the rest of the
subunits are stimulated and become active.
• Ligands can either have positive cooperativity, negative
cooperativity, or non-cooperativity.
• Positive cooperativity is the binding of oxygen to hemoglobin.
One oxygen molecule can bind to the ferrous iron of a heme
molecule in each of the four chains of a hemoglobin molecule.
Deoxy-hemoglobin has a relatively low affinity for oxygen, but when
one molecule binds to a single heme, the oxygen affinity increases,
allowing the second molecule to bind more easily, and the third and
fourth even more easily. The oxygen affinity of 3-oxy-hemoglobin is
~300 times greater than that of deoxy-hemoglobin. This behavior
leads the affinity curve of hemoglobin to be sigmoidal, rather
than hyperbolic as with the monomeric myoglobin.
24

25. • Negative
cooperativity means
that the opposite
will be true;
as ligands bind to
the protein,
the protein's affinity
for the ligand will
decrease.
25

26. Molecular Basis Of Cooperativity
• Hemoglobin is a protein with a quaternary structure. It can exist in
two quaternary states namely the tense (or T) state and the
relaxed (or R) state.
• The conformations of the individual polypeptide chains and their
relative orientations are different in the T and R states.
• Oxygenation rotates the α1β1 dimer in relation to α2β2 dimer
about 15°.
• When hemoglobin switches from T-state to R state, α1 and α2
globins move closer to each other.
• Similarly, β1 and β2 globins move closer in the R-state.These two
states are in equilibrium with each other.
• Dioxygen can bind to hemoglobin in both the states; however it has
a higher affinity for hemoglobin in the R state.
26

27. 27
Animation of
hemoglobin T-R state
transformation

28. BOHR EFFECT
• In muscles, Hb is much poor O2 binder at lower
pressures of O2.
• Then Hb passes its O2 on to Mb as required.
• The need for O2 is greatest in tissues which have
already consumed oxygen and simultaneously
produced CO2.
• The CO2 lowers the pH and the increased acidity
favours release of O2 from oxyhemoglobin to Mb.
2H20 + CO2---------- HCO3
- + H3O+
28

29. • Thus, the oxygen affinity of hemoglobin varies
with the pH of the medium This pH sensitivity is
called Bohr effect. Thus the variation of oxygen
affinity with the pH of the medium is called Bohr
effect.
• The affinity of Hb for O2 decreases with
decreasing pH.
• Blood is buffer so that the decrease in pH is very
small with accumulation of CO2 in muscles.
29

30. • Bohr effect has important physiological effect in
transporting oxygen from the lungs to the
respiring tissues and in transporting CO2
produced there back to lungs. The CO2 produced
diffuses from the muscles tissues to the
capillaries and dissolved CO forms bicarbonate
only very slowly as :
CO2 + 2H20 = HCO3
- + H30+
The enzyme carbonic anhydrase in red blood
cells accelerates the reaction so that most of CO2
in blood is carried in the form HCO3 by Hb back to
lungs where CO2 is exhaled.
30

31. CO Poisoning
• Carbon monoxide is a very dangerous gas and can cause fatal
poisoning since it binds hemoglobin preferentially over oxygen
when both are present in the lungs owing to its higher affinity
towards hemoglobin in comparison to oxygen.
• Once carbon monoxide sticks to hemoglobin forming a very bright
cherry red carboxyhemoglobin, it keeps riding around never giving
their seats up to the oxygen.
• Eventually, blood loses all of its ability to transport oxygen and
there is no way to get oxygen to your brain, heart, or other cells
which eventually stops all the biochemical reactions
• So, inhalation of even trace amount of carbon monoxide can cause
headaches, fatigue, depression and dizziness. However, if exposure
is chronic it can lead to more serious complications like heart
disease and sometimes death.
31

32. 32

33. REFERENCES
• https://epathshala.nic.in
• https://en.wikipedia.org/wiki/Hemoglobin
• https://en.wikipedia.org/wiki/Myoglobin
• Kalsi P S and Kalsi J P (2016) Bioorganic,
bioinorganic and supramolecular chemistry.
New age international publishers.
33

34. 34