HEMOGLOBIN SYNTHESIS:

A hemoglobin molecule is composed of a protein group, known

as globin, and four heme groups, each associated with
an iron atom. In the lungs, each iron atom combines reversibly
with a molecule of oxygen.
1) Heme is composed of a ring like organic compound known as
a porphyrin, to which an iron atom is attached. It is the iron
atom that reversibly binds oxygen as the blood travels
between the lungs and the tissues.
2) Globins are heme-containing proteins involved in binding,
transporting, and delivering oxygen and other nutrients.
3) heme consist of 4 percent of HB. and globin constitutes about 90 of
HB.
Heme Synthesis:
• Heme is synthesized in a complex series of steps involving enzymes in
the mitochondrion and in the cytosol of the cell.
• The first step is
• 1: formation of aminno levulinic acid [ALA]
• The second step is
• 2: formation of Porphobilinogen
• THE third step is
• 3:formation of Uroporphyrinogen
• The forth step is
• 4:formation of protoporphrinogen 3
THE fifth step is
5 : formation of protoporphyrin
THE sixth step is
6: formation of Heme .
HEME CONTAINING PROTEINS
1: HEMOGLOBIN
2:MYOGLOBIN
3:CYTOCHROMES
4: CATALASE
5:SOME PEROXIDASE
Globin Synthesis:
• Two distinct globin chains (each with its individual heme molecule)
combine to form hemoglobin.
• One of the chains is designated alpha. The second chain is called "non-
alpha".
• Globin has a chain of 574 amino acid, alpha has 141 amino acid and beta
has 146 amino acid.
• With the exception of the very first weeks of embryogenesis, one of the
globin chains is always alpha.
• The fetus has a distinct non-alpha chain called gamma. After birth, a
different non-alpha globin chain, called beta, pairs with the alpha chain.
• The combination of two alpha chains and two non-alpha chains
produces a complete hemoglobin molecule (a total of four chains per
molecule).
• 1) The combination of two alpha chains and two gamma chains form
"fetal" hemoglobin, termed "hemoglobin F".
• 2) The combination of two alpha chains and two beta chains form
"adult" hemoglobin, also called "hemoglobin A".

The pairing of one alpha chain and one non-alpha chain produces a
hemoglobin dimer (two chains). The hemoglobin dimer does not
efficiently deliver oxygen, however. Two dimers combine to form a
hemoglobin tetramer, which is the functional form of hemoglobin.
GENES THAT CODE FOR GLOBIN:
• The genes that encode the alpha globin chains are on chromosome 16.
• Those that encode the non-alpha globin chains are on chromosome 11.
• The expression of the alpha and non-alpha genes is closely balanced
by an unknown mechanism. Balanced gene expression is required for
normal red cell function. Disruption of the balance produces a disorder
called thalassemia. Thalassemia is a blood disorder passed down
through families (inherited) in which the body makes an abnormal
form or inadequate amount of hemoglobin.
• As they are protein, their synthesis occurs at RER.
COMPONENTS OF HEMOGLOBIN:
• Protein components called globin as discussed.
• Four molecule of nitrogenous substance protoporphyrin ix.
• Four iron atoms at ferrous state .
• DIPHOSPHOGLYCERATE.
(2,3-Bisphosphoglyceric acid, also known as 2,3-diphosphoglyceric
acid, is a three-carbon isomer of the glycolytic intermediate 1,3-
bisphosphoglyceric acid.) (C3H8O10P2
• (2,3-DPG; a salt in red blood cells that plays a role in liberating
oxygen from hemoglobin in the peripheral circulation). These
substances do not bind to hemoglobin at the oxygen-binding sites.