This document discusses the composition and functions of blood plasma proteins. It notes that plasma contains over 200 individual proteins that can be categorized into albumins and globulins. The major globulin categories are alpha-1, alpha-2, beta, and gamma globulins. Gamma globulins contain immunoglobulins which are antibodies that bind to antigens. The document describes the five major immunoglobulin classes - IgA, IgG, IgM, IgD, and IgE - and their properties and functions in the immune system. It also discusses other important plasma proteins like fibrinogen, complement proteins, acute phase proteins, transport proteins, and enzymes.

1. ФБОУ БГМУ ВО БГМУ
BLOOD PLASMA PROTEINS

2. Blood is a special type of liquid
connective tissue
• Parameters of blood:
• Volume - 5-6 L
• Specific weight – 1,050 – 1,060
• Osmotic pressure - 7,6 – 8,1
• pH - 7,36-7,44
• t - 38º C

3. Functions of blood
• 1. Transport
• gases - O2, CO2 respiratory function
• amino acids, fatty acids, glucose – nutritive function
• hormones – regulatory function
• waste product – excretory function
• 2. Protection, immune response
• leucocytes, antibodies, acute phase proteins
• 3. Thermoregulation
• 4. Homeostasis (maintenance of pH,
osmotic pressure…)

4. Composition of blood
Plasma
(55% of whole blood)

5. Ratio: plasma-cellular part

6. • Up to 95% of plasma volume is water. The
major solute is heterogeneous proteins (6-
8% by weight)
• (Total plasma protein – 65-85 g per L
• (estimated by biuret method)
• 4% of plasma protein is fibrinogen
• concentration in plasma – 3,5-4 g per L
• Molecular weight – 340 kD
• Glycoprotein
• Fibrinogen → fibrin → clot
• Serum is defibrinated plasma

7. There are more than 200 individual
proteins in plasma
Two families of plasma proteins
obtained by salting out:
Albumins -40-50 g per L
Globulins 20-30 g per L
The more efficient method is electrophoresis

8. Types of Electrophoresis
depending supporting medium:
• 1. filter paper electrophoresis(takes 16-18
hours, 5 bands are obtained)
• 2. Agar gel electrophoresis (1-2 h-s, 5
bands)
• 3. PAGE (polyacrylamide gel EP)
combines electrophoresis and sieving
effect, 20 fractions
• 4. immune electrophoresis followed by
antigen-antibody reaction, 40 fractions

9. Agar gel electrophoresis is
commonly used in clinical laboratory

10. Technique
• 1. Electrophoretic run is carried at pH 8,6.
Proteins are charged negatively and move
toward anode
• 2. After run is completed proteins are fixed
by methanol
• 3. Then stained using dyes
• 4. Proteins are quantified by densitometry

11. Normal proteinogram

12. In agar gel (or paper) electrophoresis
more than 200 serum proteins are
separated into 5 bands:
Albumins - 55-65 %
α1 –globulins - 4-7%
α2-globulins - 5-9%
β-globulins - 7-14%
γ-globulins - 14-22%

13. Proteinogram of patient with
myeloma (peak in γ-globulins)

14. Inflammatory (left -peak in α- and β-
globulins) in and
normal(right)proteinogram

15. α1-antitrypsin deficiency(left) and
immunodeficiency(right) state

16. Proteinogram abnormalities
Liver
diseases
Nephrotic
syndrome
Acute inflammation
Myeloma
Immunodeficiency
state

17. Heterogeneous plasma proteins
depending the function are
classified as:
1. transport proteins
• 2. proteins involved in hemostasis
• 3. antiproteases
• 4. proteins of immune system
• 5. APP - acute phase proteins
• (include proteins of classes 1-4)

18. Albumins - molecular weight – 60-70 kD
• half-life - 20 days
• Produced by liver (25% of protein synthesis in
liver, 12 g per day, used as a liver function test)
• Functions
• 1. provide of 80% of blood oncotic pressure
• 2. transport of fatty acids, bilirubin, Ca, 10% of
plasma Cu, bile acids, sulfa-drugs, antibiotics…
• 3. depot of amino acids
• liver↔ blood proteins ↔ tissues
• Therapeutic use – in burns, hemorrhages…

19. α1-globulins include
• Retinol binding protein (carries vitamin A)
• Thyroxine binding protein (T4)
• Transcortin (corticosteroids and progesterone)
• α1-antitrypsin belongs to serpins -
• serine proteases inhibitors, inhibits
• plasmin, thrombin, chymotrypsin, trypsin (80%
of plasma antiproteolytic activity)
• α1-antitrypsin deficiency is associated with
chronic obstructive pulmonary disease
(emphysema) and liver diseases
• HDL(α-lipoproteins)

20. α2 –globulins include
• Haptoglobin binds Hb released in RBC
hemolysis, preventing the loss of iron in urine
• α2 –macroglobulin – 10% of blood antiprotease
activity
• ceruloplasmin - blue due to presence of Cu –
0,32 %, 6-8 atoms of Cu per molecule, 90% 0f
plasma Cu
• An antioxidant
• ferroxidase: Fe2+→Fe3+ (incorpor. in transferrin)
• Concentration decreases in Wilson”s
disease(hepatocellular degeneration, defect of

21. β-globulins include
• LDL (β-lipoproteins)
• Transferrin presents 3% of total plasma protein
• specific iron binding protein
• 1/3 of transferrin is saturated with Fe3+(in iron
deficient anemia % of saturation lowers)
• half-life is 7 days (the better indicator of protein
turnover in liver than albumin
• fibrinogen
• CRP – C-reactive protein reacts with C-
polysaccharide of pneumococci, produced by
liver. Functions – activation of complement,

22. APP - acute phase proteins -
• Concentration may increase in 5 to 1000 folds
in inflammatory and neoplastic conditions
• Positive APP (increase in inflammation)
• – CRP, haptoglobin, fibrinogen ceruloplasmin,
serum amyloid A (more than 30 plasma
proteins)
• Negative APP (decrease in inflammation) –
albumin, thyroxine binding protein, transferrin

23. γ-globulins
include immunoglobulins -
glycoproteins which selectively bind antigens.
An antigen is the chemical structure that is
recognized as non self
by chemical nature antigens – proteins,
glycoproteins, lipoproteins, nucleoproteins…

25. Ig-functional sites
• Variable domains – antigen binding sites
• At Hinge region Ig can move to adjust for
tight binding with antigen
• carbohydrate oligosaccharide (15-18%)
• CH1, CH2 - complement binding sites
• CH3 – opsonization site, facilitating
agglutination and precipitation of antigen
molecule

26. At Hinge region Ig
can move to adjust
for tight binding with
antigen
CHO –
carbohydrate
oligosaccharide (15-
18%)
CH1 CH2 -
complement binding
sites
CH3 – opsonization
site facilitating
agglutination and
precipitation of
antigen molecule

29. There are 5 classes of Ig –
A,D,E,G,M
• Light chains (220 amino acid long) are
identical in all Ig (two types of L-chains - λ
and κ )
• Heavy chains (440 -700 amino acid long)
are specific for different classes of Ig

30. IgA (α2λ2, α2κ2) Mr weight is 160kD
• concentration in plasma – 0,8-4 g per L (20% of
plasma Ig)
• The major Ig of exocrine secretions (saliva,
milk, tears…)
• In exocrine secretions is found as a dimer

31. Dimer is more stable and
protected from proteolysis

32. IgG(γ2λ2 and γ2κ2)
Mr weight 170kD
• Concentration in blood – 8-18 g per L,
the major plasma Ig (75% of all plasma
Ig)
• provides passive immunity, the only
class of Ig are traversed across
placenta
• Functions are opsonization,
complement activation, activation of
phagocytosis

33. IgM (μ2λ2 and μ2κ2) Mr weight 170kD
• Concentration in blood – 0,6-2,8 g per L, (7%
of all plasma Ig)
• Is the first antibody to appear in the first
contact with an antigen (the primary
respond)
• The largest Ig due to formation of pentamers

34. Ig M pentamer

35. Ig D (δ2λ2, δ2κ2) Mr weight 185 kD
• concentration in blood – 0,03-0,15 g per L
(0,25 % of all plasma Ig)
• represents 1% of plasma membrane
proteins in immature B-lymphocytes)
• function is to participate in antigen
dependent differentiation of B-cells

36. Ig E (ε2λ2, ε2κ2) Mr weight 196 kD
• concentration in blood – 0,05 mg per L
• (0,002 -0,05 % of all plasma Ig)
• is associated with membranes of mast
cells and basophils
• is involved in allergic response

37. Plasma enzymes:
-Secretory (normal components of plasma –
enzymes of blood clotting, lipoprotein lipase,
pseudo choline esterase…)
-Indicatory (intracellular enzymes entering plasma
in corresponding tissue damage - AlAT, AsAT,
amylase, isozymes of LDH, Creatine Kinase )
-Excretory (are normally excreted into the bile,
increased activity in plasma signals cholestasis –
alkaline phosphatase, γ-GGT (glutamyl
transferase), leucine aminopeptidase)

38. Complement system
Is composed of about 2O plasma proteins
that act in sequential cascade
Functions:
1)Lysis of foreign cells by rupturing their
membranes
2)Opsonization – activation of phagocytosis
3)Activation of inflammation

39. Classical pathway of
complement activation

40. Связывание железа в активном центре тренсферрина