‫اﻋداد اﻟطﺎﻟﺑﺔ ﺳﺟﻰ ﻓراس ﻗﯾس‬

Lecture 8
Hemoglobin
Hemoglobin (Hb) is the iron-containing coloring pigment of red blood
cell (RBC). It forms 95% of dry weight of RBC and 30 to 34% of wet
weight. The function of hemoglobin is to carry O2 and CO2. The
molecular weight of Hb is 68,000. Average Hb content in blood is 14 to
16 g/dL. However, it varies depending upon age and sex of the
individual and the number of RBCs.

Age
At birth : 25 g/dL
After 3rd month : 20 g/dL
After 1 year : 17 g/dL
From puberty onwards : 14 to 16 g/dL
In adult males : 15 g/dL
In adult females: 14.5 g/dL
‫ﻣﺎ ﯾطرأ ﻋﻠﻰ ال‬
types of hemoglobin in Normal Adult ‫ اي ﺗﻐﯾر‬alpha
(HbA): It is the normal adult Hb. Its molecule consists of four polypeptide chains;
(alpha (α 2) , beta (β 2)). the two polypeptides α chains, contains 141 amino acid
residues, and β chains, each of which contains 146 amino acid residues. Hb A is
the predominant type of Hb in adults (95-97% of total Hb).

HbA2 2.5% of the hemoglobin is (α 2, delta (δ 2)) in which β chains are replaced
by δ chains which also contain 146 amino acid residues, but 10 amino acids differ
141 ‫ ﻋددھﺎ‬alpha ‫ال‬
from those in the β chains ‫ أﺣﻣﺎض أﻣﯾﻧﯾﺔ ح ﺗﺗﻐﯾرﺑﺎﻟﺗﺳﻠﺳل‬١٠ ‫ ﺑس ھﻧﺎﻧﺔ‬146 ‫ ﻋددھﺎ‬beta ‫و ال‬
Hb1c has a glucose attached to the terminal valine in each chain and it increases
in the blood of patients with poorly controlled ١٤٦ beta ‫ و ال‬١٤١ alpha ‫ال‬
diabetes mellitus valine ‫ﺑس اﺧﯾر اﻟﺣﻣض اﻻﻣﯾﻧﻲ ح ﯾرﺗﺑط ب ال‬
glucose ‫اﻟﻲ ﯾرﺗﺑط ﺑﺳﻛر ال‬

‫ﯾﻛون ﺑﺎﻟطﻔل‬ Fetal hemoglobin (hemoglobin F) (α 2 , gamma (γ 2)):

‫ﺣدﯾث اﻟوﻻدة‬ Its structure is similar to that of hemoglobin A except that the β chains are replaced
by γ chains; The γ chains also contain 146 amino acid residues but have 37 that
differ from those in the β chain. ‫ ﺣﻣض اﻣﻣﯾﻧﻲ ﯾﺗﻐﯾرون‬٣٧
Affinity for oxygen in case of HbF is more than that of HbA, i.e. it can take more
oxygen than HbA at low oxygen pressure. It is owing to poor binding of 2,3-DPG
by the γ polypeptide chain. Because of this, movement of oxygen from maternal to
fetal circulation is facilitated. At PO2 20 mm Hg, HbF is 70% saturated while HbA
is only 30%–35% saturated. Resistance to action of alkalies is more in HbF than
HbA. This property is used in a photoelectric calorimetric method to estimate HbF
in the presence of HbA.

Hemoglobin synthesis
The production of red blood cells and synthesis of hemoglobin depends
on the supply of iron, along with that of vitamin B 12 and folic acid.
Heme synthesis
Heme synthesis occurs in most cells of the body, except the mature
erythrocytes, but most abundantly in the erythyroid precursors.
Succinylcoenzyme A (from the tricarboxylic acid cycle) condenses with
glycine to form the unstable intermediate α-amino β-ketoadipic acid,
which is readily decarboxylated to δ-aminolevulinic acid (ALA). This
condensation requires pyridoxal phosphate (vitamin B6) and occurs in
mitochondria. Two molecules of ALA condense to form the
monopyrrole, porphobilinogen, catalyzed by the enzyme ALA
dehydrase.Four molecules of porphobilinogen react to form
uroporphyrinogen III or I. The type III isomer is converted, by way of
coproporphyrinogen III and protoporphyrinogen, to protoporphyrin. Iron
is inserted into protoporphyrin by the mitochondrial enzyme
ferrochetalase to form the finished heme moiety.
Globin synthesis
Globin synthesis occurs in the cytoplasm of the normoblast and
reticulocyte. The polypeptide chains are manufactured on the ribosomes.
Specific small soluble RNA molecules determine the placement of each
amino acid according to the code in the messenger RNA (mRNA).
Progressive growth of the polypeptide chain begins at the amino end.
This process of protein synthesis occurs on ribosomes clustered into
polyribosomes, which are held together by the mRNA. The polypeptide
chains released from the ribosomes are folded into their three-
dimensional configurations spontaneously. The complete globin
Hemoglobin synthesis

1. 2 Succinyl-CoA + 2 glycine ---> pyrrole

(‫ )ﺣﻣض اﻣﯾﻧﻲ‬glycine ‫ ﯾرﺗﺑط ب ال‬succynil co A ‫ال‬

2. 4 pyrrole ---> protoporphyrin ix

‫ ﯾﺗﺣول اﻟﻰ اﻟﻧواة اﻻﺳﺎﺳﯾﺔ ﻣﺎت‬pyrrole ‫ال‬
‫اﻟﮭﯾﻣوﻏﻠوﺑﯾن‬

3.protoporphyrin 1x + Fe ---> heme

heme ‫اﻟﻧواة ح ﺗرﺗﺑط ﺑﺎﻟﺣدﯾد ﺣﺗﻰ ﯾﻛون‬

4.Heme + polypeptide ---> hemoglobin chain

(alpha or beta)
‫ و ﯾﺳوي واﺣد ﻣن‬polypeptide ‫ ﯾرﺗﺑط ﺑﺎل‬heme‫ال‬
‫اﻟﺳﻼﺳل اﻟﻔﺎ او ﺑﯾﺗﺎ‬

5.2 alpha chains + 2 beta chains ---> Hemoglobin A

‫ ﺑﯾﺗﺎ ح ﯾرﺗﺑطون ﺳوا و‬٢ ‫ﺳﻠﺳﻠﺗﯾن اﻟﻔﺎ و‬

‫ﯾﺳوون ھﯾﻣوﻏﻠوﺑﯾن‬

‫ﻓﻘط ھذا اﻟﻣطﻠوب ﻣن اﻟﺗﻛوﯾن‬

‫ﻣﺎت اﻟﮭﯾﻣوﻏﻠوﺑﯾن‬
structure consists of four polypeptide chains formed by two dissimilar
pairs. Control of hemoglobin synthesis is exerted primarily trough the
action of heme. Increased heme inhibits further heme synthesis by
inhibiting the activity and synthesis of ALA synthase. Heme also
promoted globin synthesis, mainly at the site of chain initiation, the
interaction of ribosomes with mRNA.
Iron Metabolism
• Because iron is important for formation of Hb, myoglobin and other
substances such as cytochromes, cytochrome oxidase, peroxidase, and
catalase, it is essential to understand the means by which iron is utilized
in the body.
• The total quantity of iron in the body average 4-5 grams, about 65% of
which is in the form of Hb.
• About 4% is in the form of myoglobin, 1% is in the form of the
various heme compounds that promote intracellular oxidation, 0.1% is
combined with the protein transferrin in the blood plasma, and 15-30%
is stored mainly in the reticuloendothelial system and liver parenchymal
cells, principally in the form of ferritin. A man excretes about 1 mg of
iron each day, mainly into the feces
When iron is absorbed from the small intestine, it immediately combines
in the blood plasma with beta globulin, apotransferria to form
transferrin, which is then transported in the plasma. The iron is loosely
combined with the globulin molecule and consequently, can be released
to any of tissue cells at any point in the body. Excess iron in the blood is
deposited in all cells of the body, but especially in liver hepatocytes. In
the cell cytoplasm, it combines mainly with a protein, apoferritin to form
ferritin. The iron stored as ferritin is called storage iron. Smaller
quantities of the iron in the storage pool are stored, insoluble form called
hemosiderin. When the quantity of iron in plasma falls very low, iron is
removed from ferritin quite easily, but much less easily from
hemosiderin. When red blood cells have lived their life span and are
destroyed, the Hb released from the cells is ingested by the cells of the
monocytes-macrophage system. There free iron is liberated, and it is
mainly stored in the ferritin pool or formation of new Hb.
 Hb Compounds
There are different compounds of Hb:
1. Oxyhemoglobin: this results from combination of O2 with Hb.
Hb + O2 → HbO2
2. Carboxy Hb: this results from union of Co gas with Hb, Co gas is a
very poisonous gas even if it is present in very small amount it displaces
O2 in OxyHb so that carboxy Hb is produced, this is because of Co gas
is about 250 times greater than O2 to Hb. ‫ ﻣرة اﻗوى ﻣن اﻻﻛﻛﺳﺟﯾن‬٢٥٠ ‫ﯾرﺗﺑط‬
3. Sulfa Hb: this compound results from the combination of Hb with
sulpher compounds.
4. Carbamino Hb: this results from the combination of CO2 gas with
Hb.
Hb + CO2 → HbCO2
‫ﻧﺎﺧذ ﻣﻛﻣﻼت‬ 5. Methemoglobin: if Hb subjected to O2 in the presence of an
‫ﻏذاﺋﯾﺔ ﺟﺳﻣﻧﺎ‬
‫ﻣﺎ ﯾﺣﺗﺎﺟﮭﺎ‬
oxidizing agent, oxidation occurs and a new compound is produced is
called Meth Hb.
Met Hb Fe → Fe + Hb → HbFe
Destruction of Hb
The Hb released from the cells when they burst is phagocytosed almost
immediately by macrophages in many parts of the body, but especially
in liver (Kupffer cells), spleen and bone marrow. During the next few
hours to days, the macrophage release the iron from the Hb back into the
blood to be carried by transferrin either to bone marrow for production
of new R.B.C. or to the liver and other tissues for storage in the form of
ferritin. The porphyrin portion of the Hb molecule is converted by the
macrophages, through a series of stages, into bile pigment bilirubin,
which released into the blood and later secreted by the liver into the bile.
A high level of bilirubin in the blood causes Jaundice, a yellowish cast
in light-colored skin and the whites of eyes. Jaundice may be a sign of
rapid hemolysis or a liver diseases. The normal plasma concentration of
bilirubin is 0.5 mg/dl. The skin begins to appear jaundiced when
concentration rise 1.5 mg/dl
Jaundice:
It is the yellowish discoloration of skin and mucous membranes resulting from an
increased bilirubin concentration in the body fluids. It is detectable when plasma
bilirubin level rises above 2mg/dl. Jaundice can be classified to different types
1-Hemolytic jaundice (as a result of excessive destruction of RBCs)
2-Hepatic jaundice (as a result of damage to the liver)
3-Obstructive jaundice (as in cases of obstruction of bile ducts
The common causes of jaundice are:
1. Increased destruction of R.B.C. with rapid release of bilirubin
into blood.
2. Obstruction of the bile duct or damage to the liver cells.