1. Plasma Proteins

2. Plasma Proteins
(Cont.)
The plasma is the liquid medium of the
blood(55-60%),in which the cell
components namely
erythrocytes,leukocytes,platelets and
many proteins are suspended.
Plasma – clotting factors=Serum
Total concentration of plasma protein in
blood is 7g/dl, which in total makes 7% of
total blood volume.

3. General characteristics
of plasma proteins
All the plasma proteins are synthesized
in liver except gamma globulins which is
synthesized by Plasma cells.
Almost all the plasma proteins are
glycoproteins.
Some of the plasma proteins exhibit
polymorphism(exist in different
phenotypes) e.g α1 antitrypsin,transferrin
and hepatoglobin.

4.  The concentration of certain plasma
proteins (acute phase proteins)
increases in disease states such as
inflamation and tissue damage.These
include C-reactive proteins,hepatoglobin,
fibrinogen and α1 antitrypsin.

5.  Electrophoresis is the most commonly
employed technique for the separation
plasma proteins.
 Electrophoresis is used for the diagnosis
of certain diseases e.g multiple
myeloma,acute infections,Neprotic
syndrome etc.

6. Plasma Proteins
(Cont.)
Types
 Albumins
 Globulins
 α1-Globulins
 α1-antitrypsin
 Lipoprotein
 Orosomucoid
 Retinol binding protein
 Thyroxin binding protein

7.  α2 Globulins
 α 2-Macroglobulin
 Hepatoglobins
 Prothrombin
 Ceruloplasmin
 β Globulins
 Lipoproteins
 Transferrin
 Hemopexin

8.  γ Globulins
 Immunoglobulins.
 Fibrinogen

9. Plasma Proteins
(Cont.)
Albumins
 most abundant blood plasma protein.
 Concentration is 3.5-5.0g/dl
 Produced in the liver
 Normally constitutes about 60-80% of human
plasma protein.
 Half life is of 20 days
 Examples
 In animals Serum albumin,
ovalbumin,lactalbumin.


10. Plasma Proteins
(Cont.)
Functions
 Carriers for molecules of low water
solubility including lipid soluble
hormones, bile salts, un-conjugated
bilirubin, free fatty acids (apo-protein),
calcium ions, and some drugs like
warfarin.

11. Plasma Proteins
(Cont.)
 Metal Binding:
 A large proportion of zinc in serum is bound to
albumin. Albumin binds other divalent cations,
such as Ca, Mg, Mn, Cd, Co, and Ni.
 Fatty Acid Binding:
 Fatty acids, such as linoleic, linolenic and oleic
acid are insoluble in aqueous solutions and
must be delivered to cells by a carrier
molecule.

12. Osmotic function
 Albumin contributes to 75-80% OF TOTAL
PLASMA OSMOTIC PRESSURE(25 mm
Hg).Thus albumin plays a predominant role in
maintaing the blood volume and body fluid
distribution.
 Decrease in plasma albumin levels results in
fall in plasma osmotic pressure,leading to
enhanced fluid retention in tissue spaces
causing EDEMA.

13. Regulation of colloidal pressure
Gaw: Clinical Biochemistry; Churchill Livingstone (1999), p. 44.

14. Plasma Proteins
(Cont.)
 Mixed Disulfides or Albumin:
 Human and bovine albumins contain an
unpaired sulfhydryl at position 34 in their
primary sequences. This sulfhydryl group
often forms a covalent link with other
sulfhydryl molecules such as cysteine or
glutathione. Protect these molecules
from oxidation and improve their
availability for cells.

15. Plasma Proteins
(Cont.)
Albumins (Cont.)
 Low albumin (hypoalbuminemia) may be
caused by liver disease, nephrotic syndrome,
burns, protein-losing enteropathy,
malabsorption, malnutrition, pregnancy,
genetic variations and malignancy.
 High albumin (hyperalbuminemia) is almost
always caused by dehydration.

16. Plasma Proteins
(Cont.)
Globulin
 Some globulins are produced in the liver, while
others are made by the immune system.
 High molecular weight
 Solubility and electrophoretic migration rates
lower than for albumin
 Normal concentration in blood is 2 to 3.5 g/dl.

17. Plasma Proteins
(Cont.)
 Globular protein.
 Protein electrophoresis is used to
categorize globulins into the following
four categories:
 Alpha 1 globulins
 Alpha 2 globulins
 Beta globulins
 Gamma globulins

18. Plasma Proteins
(Cont.)
Transferrin(β globulin)
 A glycoprotein
 polypeptide chain containing 679 amino acids
 Binds iron reversibly
 molecular weight of around 80 KDa
 transferrin protein loaded with iron binds to
transferrin receptor
 transported into the cell

19. Plasma Proteins
(Cont.)
 Each transferrin molecule has the ability to
carry two iron ions in the ferric form (Fe3+).
 Protects the body against the toxic effects
of free iron.

20. Plasma Proteins
(Cont.)
 Increased serum transferrin level occurs
in iron deficiency anemia.
 An absence of transferrin in the body
occurs in a rare genetic disorder known
as atransferrinemia.

21. Plasma Proteins
(Cont.)
Ceruloplasmin (Alpha 2 globulins)
 Copper-carrying protein
 Synthesized in the liver
 Carries 90% of the copper in our plasma
 Molecular weight 151KDa .
 Low Ceruloplasmin levels: hepatic disease,
Wilson's disease.
 Elevated levels: pregnancy, acute and chronic
inflammation

22. Plasma Proteins
(Cont.)
Fibrinogen
 Fibrous protein
 Involved in the clotting of blood
 Fibrin is made from fibrinogen
 Soluble plasma glycoprotein
 Synthesized by the liver
 340 KDa glycoprotein

23. Plasma Proteins
(Cont.)
 blood plasma is 1.5-4.0 g/L
 Hexamer containing two sets of three different
chains (α, β, and γ), linked to each other by
disulfide bonds. The N-terminal sections of
these three chains contain the cysteines that
participate in the cross-linking of the chains.
The C-terminal parts of the α, β and γ chains
contain a domain of about 225 amino-acid
residues, which can function as a molecular
recognition unit.

24. Plasma Proteins
(Cont.)
 Congenital deficiency (afibrinognenemia)
 Acquired deficiency: after hemodilution.

25. Haptoglobin(Alpha 2
globulin)
 Acute phase protein.
 It binds with free hemoglobin(extracorpuscular
hemoglobin) that spills into the plasma due to
hemolysis.
 The Hp-Hb complex (155,000) cannot pass
through glomeruli of kidney while free Hb
(65,000) can.
 Hepatoglobin therefore prevents the loss of
free hemoglobin into the kidney.

26. C-REACTIVE PROTEIN (CRP)
• Major component of the acute phase response and a
marker of bacterial infection.
• Mediates the binding of foreign polysaccharides,
phospholipids and complex polyanions, as well as the
activation of complement
• <1 mg/mL in normal plasma
• Slightly elevated levels of CRP are indicative of
chronic, low-grade inflammation and have been
correlated with an increased risk of cardiovascular
disease .

27. Alpha 1
antitrypsin(Alpha1
globulin).
ASSIGNMENT.

28. IMMUNOGLOBULI
N

29.  Higher vertebrates including man,have
evolved a defense system to protect
themselves against the invasion of
foreign substances a virus,a bacterium or
a protein.The defense strategies of the
body are collectively known as
immunity.

30.  CELLULAR IMMUNITY.Mediated by T
cells.
 HUMORAL IMMUNITY.Mediated by
immunoglobulins or antibodioes
produced by the B cells.

31. Plasma Proteins
(Cont.)
 Antibodies
 Also known as immunoglobulins
 Abbreviated as Ig
 Gamma globulin proteins
 General structure of all antibodies is very
similar

32. Antibodies
Proteins that recognize and bind to a particular antigen
with very high specificity.
Made in response to exposure to the antigen.
One virus or microbe may have several antigenic
determinant sites(epitopes), to which different
antibodies may bind.
Each antibody has at least two identical sites that bind
antigen: Antigen binding sites.
Valence of an antibody: Number of antigen binding
sites. Most are bivalent.
Belong to a group of serum proteins called
immunoglobulins (Ig’s).

33. Antibody structure
Disulfide bond
 Variable & Constant
Regions
Carbohydrate
 VL & CL
 VH & CH
CL
 Hinge Region VL
CH2 CH3
CH1
Hinge Region
VH

34. Human Immunoglobulin
Classes
 IgG - Gamma heavy chains
 IgM - Mu heavy chains
 IgA - Alpha heavy chains
 IgD - Delta heavy chains
 IgE - Epsilon heavy chains

35. • L chains are one of two types
•Designated κ and λ and only
•one type is found in Ig.

36. • L and H chains are subdivided into
variable and constant regions.The regions
are composed of three-dimensionally folded,
repeating segments called domains. An L
chain consists of one variable (VL) and one
constant (CL) domain.Most H chains consist
of one variable (VH) and three constant(CH)
domains.(IgG and IgA have three CH
domains,whereas IgM and IgE have four.)

37. The variable regions are
responsible for antigenbinding ,whereas
the constant regions are responsible
for various biologic functions eg,
complement activation and binding to
cell surface receptors.

38. Immunoglobulin Classes
I. IgG
Structure: Monomer
Most abundant (75-80%).
Can traverse blood vessels.
Transfers mother’s immunity to fetus.
Mediates foreign cell destruction by
complement system.

39. Immunoglobulin Classes
II. IgM
J
Structure: Pentamer Ch
Percentage serum antibodies: 5-10% ain
Location: Blood, lymph, B cell surface
(monomer) C
Half-life in serum: 5 days 4
Complement Fixation: Yes
Placental Transfer: No
Known Functions: First antibodies produced
during an infection. Effective against microbes
and agglutinating antigens.

40. Immunoglobulin Classes
III. IgA
Structure: Dimer
Percentage serum antibodies: 10-15%
Location: Secretions (tears, saliva, intestine,
milk), blood and lymph.
Predominant antibody in the clostrum.
Half-life in serum: 6 days
Known Functions: Localized protection of
mucosal surfaces. Provides immunity to infant
digestive tract.

41. Immunoglobulin Classes
IV. IgD
Structure: Monomer
Percentage serum antibodies: 0.2%
Location: B-cell surface, blood, and lymph
Half-life in serum: 3 days
Known Functions: In serum function is
unknown. On B cell surface, act as B cell
receptor, initiate immune response.

42. Immunoglobulin Classes
V. IgE
Structure: Monomer
Percentage serum antibodies: 0.002%
Location: Bound to mast cells and
basophils throughout body. Blood.
Placental Transfer: No
Known Functions: Allergic reactions. The
IgE molecules tightly bind with mast cells
and release histamine and cause allergy.

43. Multiple Myeloma(Plasma
cell cancer).
 Abnormal Ig production
 Malignancy of a single clone of plasma
cells in bone marrow.
 Results in overproduction of
Ig’s,mostely(75%) IgG,and in some
cases(25%) IgA or IgM.
 Synthesis of normal immunoglobulins is
diminshed causing diminshed immunity.

44.  Bence jones proteins.
 These are light chains of
immunoglobulins that are synthesized in
excess.
 In about 20% of patients of multiple
myeloma,Bence jones proteins are
excreated in the urine which often
damages the renal tubules.