Plasma proteins for undergraduate medical and biochemistry students

1. Plasma Proteins
R. C. Gupta
Professor and Head
Dept. of Biochemistry
National Institute of Medical Sciences
Jaipur, India

2. BLOOD
(45% cells,
55% plasma)
Red
blood cells
(erythrocytes)
White
blood cells
(leukocytes)
Platelets
(thrombocytes)
Plasma
(water and
solutes)

3. EMB-RCG
Plasma is blood minus the
cells
Plasma contains water and
a number of solutes
The most abundant solutes
are proteins

4. The total protein concentration in plasma
is 6-8 gm/dl
Plasma contains a large number of
proteins
Some are present in very minute amounts
e.g. hormones and enzymes
These are not considered as plasma
proteins

5. EMB-RCG
Some proteins are present in plasma in
significant concentrations
They perform their functions in plasma
These are called plasma proteins

6. EMB-RCG
Some functions of plasma
proteins are of a general nature:
Maintenance of pH
Maintenance of colloid
osmotic pressure

7. Some specialised functions are
performed by specific proteins:
• Transport of hormones, vitamins,
minerals, lipids etc
• General defense against foreign
invaders
• Specific defense against antigens
• Coagulation of blood
• Fibrinolysis

8. EMB-RCG
Plasma proteins are usually
fractionated by electrophoresis
Fractionation of plasma proteins

9. EMB-RCG
Electrophoresis
separates plasma
proteins into:
Albumin
a1-Globulins
a2-Globulins
b-Globulins
g-Globulins
‒ Albumin
‒ a1-Globulins
‒ a2-Globulins
‒ b-Globulins
‒ g-Globulins
‒
+

10. EMB-RCG
More sensitive techniques separate the
b-globulins into b1- and b2-globulins
Albumin Globulins
b1 b2a1 a2
g

11. EMB-RCG
Each globulin fraction comprises a number
of proteins
All the plasma proteins except g-globulins
are synthesized in liver
The g-globulins are synthesized in and
secreted by plasma cells

12. Most abundant protein in plasma
Concentration is 3.5 - 5.5 gm/dl
Synthesized exclusively in liver
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Albumin
Half-life approximately 20 days

13. COP of plasma is mostly
due to proteins
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Proteins are the major
colloids in plasma
Albumin is responsible for
75% of COP of plasma
Colloid osmotic
pressure
(COP)
75%
25%
Albumin
Others

14. Albumin is made up of a
single polypeptide chain
of 585 amino acids
Its molecular weight is
69,000
EMB-RCG

15. Functions of albumin
• Vehicle for transferring amino acids
from liver to extra-hepatic tissues
• Carrier of free fatty acids, calcium,
copper, unconjugated bilirubin, lipophilic
hormones etc
• Also carries drugs e.g. aspirin,
phenytoin, dicoumarol, sulphonamides
etc

16. Liver diseases due to decreased
synthesis of albumin
Renal diseases due to loss of
albumin in urine
Kwashiorkor due to severe
dietary deficiency of proteins
Hypoalbuminaemia can occur in:

17. Hypoalbuminaemia decreases the
colloid osmotic pressure of plasma
This can result in oedema
EMB-RCG

18. Another protein that can bind all the
ligands that albumin can bind
Smaller than albumin and moves
ahead of albumin on electrophoresis
Present in much lower concentration
than albumin
EMB-RCG
Prealbumin

19. Globulins
EMB-RCG
Globulins comprise several
fractions:
• a1-Globulins
• a2-Globulins
• b-Globulins
• g-Globulins

20. a1-Globulins
EMB-RCG
a1-Globulins include:
• a-Lipoprotein (HDL)
• Thyroxine-binding globulin (TBG)
• Corticosteroid-binding globulin (CBG)
• Retinol-binding protein (RBP)
• a1-Antitrypsin
• a1-Acid glycoprotein
• a-Fetoprotein

21. EMB-RCG
a-Lipoprotein (HDL) transports
cholesterol from periphery to liver
Thyroxine-binding globulin (TBG)
transports thyroid hormones
Corticosteroid-binding globulin (CBG)
transports steroid hormones
Retinol-binding protein (RBP) transports
vitamin A

22. EMB-RCG
a1-Antitrypsin is now called a1-anti-
proteinase
It is an inhibitor of serine proteases e.g.
trypsin, elastase etc
An important function of a1-antitrypsin is to
prevent destruction of elastin in lungs
a1-Antitrypsin

23. EMB-RCG
Small amounts of elastase are released in
lungs continuously from naturally dying
neutrophils
Much larger amounts are released in
pulmonary infection as neutrophils
accumulate at the site of infection
a1-Antitrypsin binds to elastase and
prevents its proteolytic action

24. EMB-RCG
An inherited deficiency of a1-antitrypsin
results in unchecked action of elastase on
elastin
Destruction of elastin decreases the
elasticity of lungs resulting in emphysema

25. EMB-RCG
Smokers with a1-antitrypsin deficiency are
particularly prone to emphysema
Cigarette smoke converts a critical
methionine residue of a1-antitrypsin into
methionine sulphoxide
This prevents the binding of a1-antitrypsin
to elastase

26. EMB-RCG
a1-Acid glycoprotein is another acute
phase protein
These are released in acute infections
a1-Antitrypsin belongs to the group of
acute phase proteins (or reactants)

27. EMB-RCG
Acute phase proteins help the immune
system in fighting against infectious agents
They also help in clearing up the debris
from the site of infection
Release of acute phase proteins is induced
by some interleukins secreted by macro-
phages and T lymphocytes

28. EMB-RCG
a-Fetoprotein (AFP) is synthesized in
foetal life but not after birth
It is synthesized in some cancers as the
cancer cells revert to the undifferentiated
type
Therefore, a-fetoprotein is used as a
tumour (cancer) marker
a-Fetoprotein

29. a2-Globulins
EMB-RCG
a2-Globulins include:
• Ceruloplasmin
• Haptoglobin
• a2-Macroglobulin

30. EMB-RCG
A copper-containing protein
90% of plasma copper is tightly
bound to ceruloplasmin
Rest is loosely bound to albumin
Ceruloplasmin

31. EMB-RCG
Ceruloplasmin was believed to be a
copper carrier in the past
But copper bound to ceruloplasmin is
not released easily
Hence the carrier function is performed
by albumin

32. EMB-RCG
Ceruloplasmin possesses ferroxidase
activity
Its real function is to oxidise ferrous
iron to the ferric form
Is also an acute phase protein

33. Another acute phase protein
Can bind free haemoglobin (Hb)
Haptoglobin

34. Hb released into plasma from ruptured
RBCs can easily pass through glomeruli
This can clog tubular lumen
It can also cause loss of iron from the
body

35. EMB-RCG
Haptoglobin binds free haemoglobin
Combined size of the two is too big to
pass through glomeruli
This prevents leakage of haemoglobin
into glomerular filtrate and loss of iron

36. EMB-RCG
a2-Macroglobulin is a general protease
inhibitor
It inhibits coagulation and fibrinolysis
a2-Macroglobulin levels are increased in
nephrotic syndrome
a2-Macroglobulin

37. b-Globulins
EMB-RCG
b-Globulins include:
• b-Lipoprotein (LDL)
• Transferrin
• Complement components C1q and C3
• Haemopexin
• C-Reactive protein (CRP)

38. EMB-RCG
b-Lipoprotein (LDL) transports cholesterol
from liver to periphery
Transferrin transports iron
Complement components help the immune
system in fighting against infections

39. EMB-RCG
Binds free haem
If haem enters plasma, it is freely
filtered by the glomeruli
This can lead to loss of iron from the
body
Haemopexin

40. EMB-RCG
Haemopexin binds haem released in
plasma
This prevents glomerular filtration of
haem and loss of iron

41. EMB-RCG
So named because it reacts with C
polysaccharide
C Polysaccharide is present in the
capsule of pneumococci
C-Reactive protein (CRP)

42. EMB-RCG
CRP is an acute phase protein
It can stimulate the classic
complement cascade upon entry
of any pathogen in the body
Raised CRP concentration in plasma
shows the presence of some infection
in the body

43. EMB-RCG
g-Globulins act as antibodies
Also known as immunoglobulins as
they perform an immune function
g-Globulins

44. EMB-RCG
Is an acute phase protein
Is converted into fibrin during
coagulation
Several fibrin molecules aggregate to
form the clot
Fibrinogen
Is one of the coagulation factors

45. Fibrinogen
Fibrin monomer
Fibrin dimer
Fibrin polymer
Fibrin polymer
cross-linked