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Lec - 12 Hemoglobin-3

Hemoglobin is an iron-containing protein in red blood cells that transports oxygen throughout the body. It is composed of four polypeptide chains and a heme group, which binds oxygen. Hemoglobin levels vary at different stages of life and are higher in males compared to females in adulthood. It binds and transports oxygen through a cooperative binding mechanism and also transports carbon dioxide by forming carbaminohemoglobin. Abnormal hemoglobins can result in hemoglobinopathies or thalassemias.

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19 views20 pages

Lec - 12 Hemoglobin-3

Hemoglobin is an iron-containing protein in red blood cells that transports oxygen throughout the body. It is composed of four polypeptide chains and a heme group, which binds oxygen. Hemoglobin levels vary at different stages of life and are higher in males compared to females in adulthood. It binds and transports oxygen through a cooperative binding mechanism and also transports carbon dioxide by forming carbaminohemoglobin. Abnormal hemoglobins can result in hemoglobinopathies or thalassemias.

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andrea
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Hemoglobin

Structure, synthesis, types,


functions, catabolism
MUST KNOOW
Hemoglobin
◼ Red, oxygen-carrying pigment in the RBC
◼ 4 subunits; each with Heme conjugated to Globin
◼ Heme contains IRON (in ferrous form); Has a
porphyrin ring structure
◼ 4 pairs of Globin (2 & 2 in adults) chains; each
attached to a heme moiety
◼ Adult Hemoglobin written as HbA(α2β2)
the best in capturing O2
◼ Fetal hemoglobin is HbF(α2γ2)
Normal values
◼ Umbilical cord blood: 16.5 G/dL
◼ Newborn: 18.5 G/dL (due to transfusion of red blood
cells form placenta & hemo- concentration)
◼ Marked fall for 2 weeks; 12 G/dL at 3rd month
◼ Rises again at the end of 1st year towards adult
values
◼ Adult male: 13- 18 G/dL (average 15.5)
◼ Adult female: 11.5-16.5 G/dL (average 14)

# clinical practice guidelines for msian(important to know)


Hemoglobin concentration at different ages

I.U life Weeks Months Years Decades

18.5
Adult values

16.5 15.5
Male

14
Female

12.5

0 2 4 1 10 20 40 60 80
Diagrammatic representation of a hemoglobin molecule,
showing 4 subunits; 2α and 2β polypeptide chains, each
containing a heme moiety

β β

HEME

α α
Synthesis of hemoglobin
Heme synthesis occurs in a series of steps:
◼ Condensation of succinyl CoA & glycine

◼ Formation of protoporphyrin III with 4 pyrole


rings
◼ Incorporation of ferrous iron into
protoporphyrin III
Heme molecules combine with globin chains
to form hemoglobin
Functions of hemoglobin
◼ Oxygen transport –as
Oxyhemoglobin
◼ Carbon dioxide transport- as
carbaminohemoglobin
◼ Buffer- mops H+ during CO2
transport
Role of Hb in O2 transport
Reactions with Oxygen
◼ O2 binds reversibly with Fe2+ of Hb to from
oxyhemoglobin (Hb4O8)
◼ Extent of binding (% saturation) determined by PO2

◼ Shows cooperative binding

◼ Affinity influenced by pH, PCO2, temperature &

2,3-DPG content of red cells


◼ 1 gram of Hb can carry up to 1.34 mL of O2, when fully
saturated
◼ A total of 4 molecules of O2 bind to a molecule of Hb
Steps of oxygenation

◼ Hb4 + O2 → Hb4O2

◼ Hb4O2 + O2 → Hb4O4

◼ Hb4O4 + O 2 → Hb4O6

◼ Hb4O6 + O2 → Hb4O8
Effects of oxygenation
◼ The insertion of oxygen to the iron of heme causes
distortion of globin chains & the quaternary structure
of hemoglobin changes from TENSE/TAUT (T) state
to RELAXED (R) state
◼ Binding of one molecule of O2 favors the binding of
subsequent 3 molecules
◼ Oxygenation reduces the buffering capacity of Hb &
releases H+ ; favors CO2 release at lungs
Role of Hb in CO2 transport
◼ CO2 binds to the NH2 groups of globin
to from carbaminoHb
R-N-H + CO2 = R-N-COO- + H+
H H
◼ Formation of carbaminoHb makes
oxygenation more difficult; Oxygen is
released from Hb (Bohr effect)
Buffering function of Hb
◼ Deoxyhemoglobin is a better buffer; binds to
H+ during CO2 transport; favors CO2 transport
form tissues to lungs
◼ Oxygenation reduces the buffering capacity
of Hb & releases H+ ; favors CO2 release at
lungs
◼ Buffering by Hb minimally alters the pH of
venous blood
Fetal Hemoglobin (HbF)
◼ Contains globin chains 2α and 2γ polypeptide
chains (α2γ2)
◼ Normally replaced by HbA soon after birth
◼ Binds 2,3-DPG less avidly → O2 content at
any given PO2 is greater than that of HbA →
facilitates O2 movement from maternal to
fetal circulation
Hemoglobin derivatives
Methemoglobin
◼ Iron is converted into ferric form when blood is
exposed to drugs & oxidizing agents
◼ Is dark-coloured; causes a dusky discolouration of
skin resembling cyanosis
◼ Red cell metabolism normally keeps iron in ferrous
state
◼ Congenital absence of the enzyme causes
hereditary methemoglobinemia
Hemoglobin derivatives
Carboxyhemoglobin (carbon monoxyHb)
◼ Hb has much greater affinity (200 times) for
carbon monoxide than for oxygen
◼ When in large concentration in blood, CO
displaces oxygen on Hb → decreases O2 -
carrying capacity of blood
◼ CO binds exactly where oxygen binds to
heme
Glycosylation of hemoglobin
◼ HbA1c; Hb that is nonenzymatically glycosylated
(glycated) by the glucose that enters erythrocytes
◼ Normal 5%
◼ increases in poorly controlled diabetes mellitus since
the amount formed is proportional to the plasma
glucose concentration
◼ Reflects the average glucose levels over the
preceding 6-8 weeks & serves as an index of long
term control of diabetes mellitus
Myoglobin
◼ O2-binding pigment found in red skeletal
muscles, specialized for sustained
contraction
◼ Binds 1 molecule of O2 per mole (not 4)
◼ Takes up O2 readily, but releases O2 only at
PO2 low values
◼ Provides O2 to muscles even when blood
flow is cut off
◼ Contains 3% of body iron
Abnormalities in Hb production
Hemoglobinopathies:
◼ Production of abnormal polypeptide chains,
e.g. HbC, E, I, J, S
◼ E.g.. In HbS- α chains are normal; β chains
are abnormal (Sickle cell disease)
◼ Sickle cell is an inherited disorder

◼ HbS polymerizes at low PO2→ Sickle shaped


red cells → Hemolysis → Anemia
Abnormalities in Hb production
Thalassemias:
◼ Normal chains produced in decreased amounts
or absent
◼ Hereditary

◼ α Thalassemias (decreased or absent α chains)

◼ β Thalassemias (decreased or absent β chains)

◼ Fetal Hb persists after birth→ Anemia


Hemoglobin catabolism
◼ Macrophage system (in spleen) destroys senile red
cells
◼ Hb molecule is split into globin & heme-derivative,
Biliverdin & then to Bilirubin (yellow pigment)
◼ Bilirubin circulates in blood bound to plasma albumin
since it is lipid soluble
◼ Normal concentration: 0.2-0.8 mg/dL
◼ Bilirubin excreted in bile after getting water-soluble by
hepatic conjugation
◼ Bilirubin converted to urobilinogens (colorless) in GIT
& excreted (mainly in stools; little in urine)

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