Biomedical Science 2

Makassar, 9th March 2011

Department of Biochemistry
Faculty of Medicine UNHAS

Introduction
Plasma proteins
Membrane of erythrocytes
Structure and function of Hemoglobin
Metabolism of Erythrocytes
Metabolism of Leukocytes
Clinical correlations

 Human

blood constitutes about 8% of the

bodysweight
Consists of cells and cell fragments in an
aqueous medium, the blood plasma
The proportion of cellular elements, known
as hematocrit, in the total volume is
approximately 45%

 The

blood plasma is an aqueous solution

of electrolytes, nutrients, metabolites,
proteins, vitamins, trace elements, and
signaling substances
The fluid phase of coagulated blood is
known as blood serum
It differs from the plasma in that it lacks
fibrin and other coagulation proteins

 Quantitatively,

proteins are the most

important part of the soluble components
of the blood plasma
With concentrations of between 60 and 80
g/L, they constitute approximately 4% of
the bodys total protein

 Some

100 different proteins occur in

human blood plasma.
Based on their behavior during
electrophoresis they are broadly divided
into five fractions: albumins and 1, 2,
and -globulins

 Under

the microscope, the red blood cell appears

to be a red disc with a pale central area (biconcave
disc)
The biconcave disc shape serves to facilitate gas
exchange across the cell membrane
The membrane proteins:
maintain the shape of the red blood cell
allow the red blood cell to traverse the capillaries with very

small luminal diameters to deliver oxygen to the tissues

 The

interior diameters of many capillaries

are smaller than the approximately 7.5m
diameter of the red cell
The spleen is the organ responsible for
determining the viability of the red blood
cells
Erythrocytes pass through the spleen 120
times per day

 The

elliptical passageways through the

spleen are approximately 3m in diameter,
and normal red cells traverse them in
approximately 30 seconds
Damaged red cells that are no longer
deformable become trapped in the
passages in the spleen, where they are
destroyed by macrophages

 On

the cytoplasmic side of the membrane,

proteins form a two-dimensional lattice that
gives the red cell its flexibility
The major proteins are spectrin, actin,
band 4.1, band 4.2, and ankyrin.

 The

most important task of the red blood

cells (erythrocytes) is to transport
molecular oxygen (O2) from the lungs into
the tissues, and carbon dioxide (CO2) from
the tissues back into the lungs
To achieve this, the higher organisms
require a special transport system, since
O2 is poorly soluble in water

 Only

around 3.2 mL O2 is soluble in 1 L

blood plasma. By contrast, the protein
hemoglobin (Hb), contained in the
erythrocytes, can bind a maximum of 220
mL O2 per liter70 times the physically
soluble amount
The Hb content of blood:
140180 g/L in men
120160 g/L in women

 Adult

hemoglobin is a tetrameric
hemeprotein (quartenery structure) found
in erythrocytes where it is responsible for
binding oxygen in the lung and
transporting the bound oxygen throughout
the body where it is used in aerobic
metabolic pathways
The tetramers are composed of pairs of
two different polypeptide subunits
The subunits are -, -, -, -chain

The haemoglobin molecule is a tetramer consisting of 4 polypeptide

chains, known as globins, which are usually:
2 alpha chains that are each 141 amino acids long
2 beta chains that are each 146 amino acids long
Attached to each chain is an iron-containing molecule known as haem

 Adult

hemoglobin is a tetrameric hemeprotein

(HbA1, 22, 97%), (HbA2, 22, 2-3%)
Two other forms occur during embryonic and
fetal development
the first three months, embryonic hemoglobins

are formed, with the 22 and 22

up to the time of birth, fetal hemoglobin then
predominates (HbF, 22)
during the first few months of life, it is replaced
gradually by HbA

Oxygenated dan Deoksigenated Hemoglobin

The subunit of deoxyhemoglobin are held
together by salt bonds between the
polypeptide
Upon oxygenation the salt bonds break
and a new set of hydrogen bonds form
The interactions between the subunits are
weaker in oxyhemoglobin than in
deoxyhemoglobin

Methemoglobin

The heme iron is ferric rather than ferrous

Can neither bind nor transport O2
Normally, the enzyme methemoglobin reductase
reduces the Fe3+ of methemoglobin to Fe2+
Methemoglobin can arise by oxidation of Fe2+ to
Fe3+ as a side effect of agents such as
sulfonamides, from hereditary hemoglobin M, or
consequent to reduced activity of the enzyme
methemoglobin reductase

 Mature

erythrocytes contain no intracellular

organelles, so the metabolic enzymes of the
red blood cell are limited to those found in
the cytoplasm
In addition to hemoglobin, the cytosol of the
red blood cell contains enzymes necessary
for the prevention and repair of damage
done by reactive oxygen species and the
generation of energy

 Erythrocytes

can only generate adenosine

triphosphate (ATP) by glycolysis
The ATP is used for:
ion transport across the cell membrane (primarily

Na+, K+, and Ca2+)

the phosphorylation of membrane proteins
the priming reactions of glycolysis
Erythrocyte

glycolysis also uses the

Rapaport-Luebering shunt to generate 2,3bisphosphoglycerate (2,3-BPG).

The Respiratory Burst

When neutrophils and other phagocytic cells
engulf bacteria, they exhibit a rapid increase
in oxygen consumption known as the
respiratory burst
This phenomenon reflects the rapid utilization
of oxygen and production from it of large
amounts of reactive derivatives, such as
O2, H2O2, OH, and OCl (hypochlorite
ion)
Some of these products are potent icrobicidal
agents.

The mutated
hemoglobin tends to
aggregate in the
deoxygenated form
This leads to sickleshaped distortion of the
erythrocytes and
disturbances
of O2 transport (sicklecell anemia)

 Koolman,

J.; Roehm, KH. Color Atlas of

Biochemistry, 2 ed. Thieme, 2004
Lieberman, M., Marks, DA. Marks Basic
Medical Biochemistry a Clinical Approach 3rd
ed. Lippincott Williams and Wilkins, 2009
Meisenberg, G., Simmons, WH. Principles of
Medical Biochemistry, 2 ed. Mosby Elsevier,
2006
Murray, RK., Red and White Blood Cells in
Harpers Ilustrated Biochemistry, Murray, RK.,
Granner, DK., Rodwell, VW(editors), 28th ed.,
2009