HEMOGLOBIN (Hematology 1, Week 7)

HEMOGLOBIN FUNCTION AND STRUCTURE

- Hemoglobin is red globular protein,
which have a molecular weight of
about 64,000 and compromise almost
one third of the weight of a red cell.
Each red cell contains approximately
640 million Hb molecules. 1. Four identical heme groups, each consisting
- Hemoglobin's main function is to
transport oxygen from the lungs to
tissues and transport carbon dioxide
from the tissues to the lungs for
exhalation.
- Hemoglobin is an oxygen transporting
protein contained within erythrocytes
The heme portion of hemoglobin
gives erythrocytes their characteristic
red color.
- Hemoglobin is composed of four of a protoporphyrin ring and ferrous (Fe 2+)
subunits. Each subunit with heme and iron
globin 2. Four globin (polypeptide) chains
1 Heme:1 moles of Oxygen 3. A tetramer of four globin polypeptide
1Hb: 4 moles of of Oxygen chains, with a heme molecule attached to
- Each subunit contains 1 heme and 1 each chain
globin HEMOGLOBIN SYNTHESIS/PRODUCTION
1. HEME - iron-chelated porphyrin
ring which functions as a prosthetic
group (nonamino acid group)
#PROTOPORPHYRIN IX - tetrapyrrole
ring with a ferrous iron inserted into
the center
"1 heme can carry 1 molecule of
oxygen bound to the central ferrous
iron
- 1 hemoglobin = 4 molecules of oxygen

1. 65 % hemoglobin synthesis occur in

immature nRBCs
2. 35 % hemoglobin synthesis occur in
reticuloytes
 3. Heme synthesis occurs in the
mitochondria of normoblasts and is
dependent on glycine, succinyl
coenzyme A, Aminolevulinic acid
synthethase, and vitamin B6
(pyridoxine)
4. Heme leaves the mitochondria to
combine with a globin chain in the
cytoplasm
5. Globin synthesis occurs in the
ribosome, and it is controlled on
chromosome 16 for alpha and zeta
chains and chromosome 11 for all
other chains
6. Globin chain are released from the
polyribosomes and combine with
heme molecules released from the
mitochondria.
7. Rubricyte = first stage of hemoglobin
synthesis
8. Reticulocytes = last stage capable of
hemoglobin synthesis
IRON KINETICS
 Iron is the most abundant transition
metal in the body
 Most iron in the body is in
Hemoglobin and must be in the
ferrous state to be used. Ferrous iron
binds to oxygen for transport to lungs
and body tissues. Ferric iron (Fe 3+) is
not able to bind to hemoglobin, but
does bind to transferring
 Iron is an essential mineral and is not
produced in the body
 Normal daily diet contains about
15mg iron and only 1-2mg of iron is
absorbed in the duodenum and upper
jejunum
 In the duodenum, dietary free iron is
reduced to ferrous iron and taken up
from the intestinal lumen into the
enterocytes by the iron transport
protein Divalent monotransporter 1
(DMT)
 Once absorbed, iron may be stored as
ferritin in the enterocytes or exported
into the circulation by another iron
transport protein, FERROPORTIN
(Fpn1)
 In the plasma, ferric iron binds to
transferrin which is delivered into
cells by binding to transmembrane
glycoprotein the transferrin receptors
(TfR)
 Hepcidin, a liver-produced peptide
hormone, is the master regulatory
hormone of systemic iron
metabolism. The interaction of
hepcidin with the plasma iron
transporter, ferroportin, coordinates
iron acquisition with iron utilization
and storage.
 Hepcidin deficiency causes common
iron overload syndromes but
overexpression of hepcidin is
responsible for microcytic anemia
(anemia of chronic inflammation).
HEPCIDIN - It regulates the transport of
iron from enterocyteMinto the circulation
by binding through ferroportin.
Two storage forms of iron.
A. Ferritin = Major storage form, water HEMOGLOBIN DERIVATIVES
soluble, considered as an acute phase
reactants. Oxyhemoglobin
B. Hemosiderin = Second storage form of
iron, water insoluble.

- Hemoglobin with Ferrous + oxygen

- Seen in arterial circulation (RELAXED
STATE)

Deoxyhemoglobin
- Hemoglobin with Ferrous but no
Oxygen
- Seen in venous circulation (TENSED
STATE)

Carboxyhemoglobin
- Hemoglobin with ferrous and carbon
monoxide CO; hemoglobin has
200x/240x
- more affinity for CO than 02
- Carbon monoxide will bind with Hb
even if its concentration in the air is
extremely low (eg 0.02 - 0.04 %)
- Cannot bind and carry oxygen
- Increasing concentration of HbCO will
shift the ODC (Oxygen dissociation
curve) to the left, thus adding to
anoxia
 - Light sensitive and imparts a typical - It can also combine to Carbon
brilliant CHERRY RED COLOR to the monoxide to form
blood carboxysulfhemoglobin
- Chief sources of the gas are gasoline - CANNOT BE REDUCED BACK TO
motors, illuminating gas, gas heaters, HEMOGLOBIN and it remains in the
defective stoves, and smoking of cell until break down
tobacco - Quantitated by spectrophotometry
- Quantitated by differential
spectrophotometry or by gas
chromatography

Methemoglobin/Hemiglobin
- Hemoglobin with Fe 3+ (ferric) ;
cannot transport oxygen
- Cause chocolate brown discoloration
of blood
- Causes Cyanosis and functional
anemia if present in high enough
concentration
- Sources: Chemical or drugs such as
chlorate, nitrate, and nitrite
- Quantitated by spectrophotometry
- An abnormal hemoglobin (Hb M) may
also be responsible for
methemoglobinemia noted at birth or
first months.

Sulfhemoglobin
- Hemoglobin with S; cannot transport
Oxygen
- During oxidation of hemoglobin,
sulfur (from some source, which may
vary) is incorporated into heme rings
of hemoglobin, resulting in a green
hemochrome
- Blood is mauve-lavender in
sulfhemoglobinemia
- Usually reported in following
situations:
 Patients under prolonged
treatment with sulfonamide
or aromatic amine
compounds ex. Pnenacitin
 Patients with severe
consupation
- In cases of bacteremia caused by
Clostridium perfringens
- In condition known as enterogenous
cyanosis