Porphyrins serve as prosthetic groups for proteins involved in oxygen transport and other functions. Hemoglobin contains heme, an iron-containing porphyrin, at the center of each subunit. Heme synthesis involves several steps beginning with the condensation of glycine and succinyl-CoA to form 5-aminolevulinate. Regulation occurs through feedback inhibition by heme. Hemoglobin transports oxygen through a sigmoidal binding curve conferred by cooperativity between subunits. Pathologies can result from oxidation, genetic mutations like sickle cell anemia, or defects in subunit synthesis as seen in thalassemias.

1. G.H. Raisoni University
DhodaBorgaon, vil.saikheda, M.P.
HAEMOGLOBIN
PRESENTED BY:
DISHA PRALHAD ANKAR
M.SC 3rd semester
Department of chemistry

2. CONTENT
❑ 1. Synthesis of Porphyrins
❑ 2. Regulation of Heme synthesis
❑ 3. Hemoglobin Structure and Function
❑ 4. Hemoglobin Pathology

3. •
PORPHYRINS SERVE AS PROSTHETIC GROUPS FOR PROTEINS THAT FUNCTION IN OXYGEN TRANSPORT
(HEMOGLOBIN AND MYOGLOBIN),
• breakdown of peroxide (catalase),
• electron transport (cytochromes a, b and c)
• hydroxylation (cytochrome P450)
• nitric oxide synthase and light absorption (chlorophyll).
• These are heterocyclic ring structures that include four pyrrole rings joined together
through carbon (methyl) bridges.
▶The most abundant porphyrins in nature are found in hemoglobin and the
chlorophylls.
▶In the center of porphyrins a metal atom is chelated to the nitrogen atoms of
the pyrrole units.
▶In heme and related porphyrins this atom is iron. In chlorophyll the metal atom is
magnesium.

4. Structure of Heme

5. The first and rate limiting reaction in porphyrin synthesis is the reaction catalyzed by
5-aminolevulinate synthase:
3 2 2 2
2
glycine + succinyl CoA --> NH +-CH -CO-CH -CH -COO- +CO +CoA
5 –aminolevulinate Pyridoxal phosphate is a cofactor for 5-aminolevulinate synthase (d- aminolevulinate
synthase, ALA synthase).
Synthesis of 5-aminolevulinate synthase is inhibited by heavy metal ions and there is a feedback
inhibition exerted by heme.
❖In second reaction two molecules of 5-aminolevulinate condense to form the monopyrrole, porphobilinogen.
❖The combination of four porphobilinogen molecules gives a linear tetrapyrrole and is accompanied by the loss
of four molecules of ammonia .
❖Ring closure catalyzed by uroporphyrinogen synthase and isomerization gives uroporphyrinogen III.
❖Further intermediates in the synthesis of heme are coproporphyrinogen III, protoporphyrinogen IX and
protoporphyrin IX.
❖The conversion of protoporphyrin IX to heme is catalyzed by ferrochelatase.
The first reaction and the last three reactions of heme synthesis occur in mitochondria with the other four
reactions being in the cytosol.
REGULATION OF HAEMOGLOBIN SYNTHESIS

6. PORPHYRIN: CYCLIC MOLECULE
FORMED BY LINKAGE OF FOUR PYROL
RINGS THROUGH METHYLENE BRIDGES
methylene
group

9. Porphobilinogen
Synthase
ALA dehydratase
ALA
SYNTHASE

10. Ferrochelatase

11. Oxygen transport is mediated by two heme proteins, myoglobin and
hemoglobin.
Myoglobin occurs in muscle and has a single polypeptide chain.Hemoglobin
occurs in red blood cells and has four polyeptide chains. Hemoglobin A is the
major type in adults and has two alpha and two beta chains. Each subunit has a
hydrophobic pocket containing the heme unit.
The oxygen binding curve for myoglobin is a rectangular hyperbola whereas
the oxygen binding curve for hemoglobin is sigmoidal in shape.
Myoglobin has a greater affinity for oxygen than hemoglobin.
The sigmoidal curve for oxygen binding to hemoglobin is an indication of
the cooperativity which exists in the binding of the four oxygen molecules.
The binding of oxygen to hemoglobin is decreased by a decrease in pH (Bohr
effect) and by an increase in the level of 2,3-bisphosphoglycerate.
3. Haemoglobin structure and functions

14. Unlike the iron in cytochromes which is alternately reduced and oxidized
as part of the mechanism of action, the iron in hemoglobin must be
maintained in the reduced state for the transport of oxygen.
Oxidation of the iron of hemoglobin from the Fe2+ to the Fe3+ state
results in the formation of methemoglobin.
Oxidation of hemoglobin to methemoglobin can be caused by a number
of agents including nitrite and some drugs. The reverse of this process
can be achieved by several NADH or NADPH-linked enzymes.

15. 1.Glucosylation of hemoglobin occurs in diabetes mellitus and may
serve to measure chronic elevation of blood glucose levels.
2.One of the most important hemoglobinopathies of genetic origin
is sickle cell anemia. This occurs when the individual is in a
substitution of valine for glutamate in the beta subunits. There is
hemolytic anemia, painful crises and poor circulation.
3.The thalassemias are a group of hereditary diseases in which
there are defects in the synthesis of either the alpha or the beta
chains.
4.Carbon monoxide binds to hemoglobin more tightly than
oxygen and it prevents oxygen release.
4. HAEMOGLOBIN PATHOLOGY

17. Thank you