1. Plasma Proteins

2. Overview: Electrophoretic patterns of plasma proteins
Functions and characteristics of plasma proteins
Measurement of plasma proteins and diagnosis of diseases
Acute phase proteins

3. Plasma Proteins (pps) Plasma contains >300 different proteins
Many pathological conditions affect level of pps
Mostly synthesized in the liver
Some are produced in other sites

4. GENERAL PROPERTIES OF PLASMA PROTEINS
MOST ARE SYNTHESIZED IN THE LIVER
Exception: -globulins – synthesized in plasma cells
Synthesized as pre-proteins on membrane-bound polyribosomes; then they are subjected to posttranslational modifications in ER and Golgi apparatus
ALMOST ALL OF THEM ARE GLYCOPROTEINS
Exception: albumin
They have characteristic half-life in the circulation (albumin – 20 days)
Many of them exhibit polymorphism (immunoglobulins, transferrin…)

6. Fractions of plasma proteins
Rel. amount (%)
c (g/l)
Albumins: albumin, pre-albumin (transthyretin)
52 – 58
34 – 50
1-globulins: thyroxin-binding globulin, transcortin, 1-acid glycoprotein, 1-antitrypsin, 1-lipoprotein (HDL), 1-fetoprotein
2.4 – 4.4
2-4
2-globulins: haptoglobin, macroglobulin, ceruloplasmin
6.1 – 10.1
5 – 9
-globulins: transferrin, hemopexin, lipoprotein (LDL), fibrinogen, C-reactive protein, C3 and C4 components of the complement system
8.5 – 14.5
6 – 11
-globulins: IgG, IgM, IgA, IgD, IgE
10 – 21
8 – 15

7. Types of Plasma Proteins
 Prealbumin
Albumin
α1-Globulins:
a1-Antitrypsin, α-fetoprotein
α2-Globulins:
Ceruloplasmin, haptoglobin
β-Globulins:
CRP, transferrin, β2-microglobulin
γ- Globulins

8. ImportantTypes of plasma proteins
Albumin
Globulins
a-globulins : a1 a a2-globulins
b-globulins: b1 a b2-globulins
g-globulins
Fibrinogen
Under different pathological conditions the protein levels depart from the normal range.

9. FUNCTIONS OF PLASMA PROTEINS
TRANSPORT OF SUBSTANCES : e.g.
albumin – fatty acids, bilirubin, calcium, drugs
transferin – iron
cerulplasmin – copper
transcortin – cortisol, corticosteron
lipoproteins – lipids
haptoglobin – free hemoglobin
thyroxin binding globulin – thyroxin
retinol binding protein - retinol

10. FUNCTIONS OF PLASMA PROTEINS (cont.)
OSMOTIC REGULATION:
Plasma proteins are colloidal and non-diffusable and exert a colloidal osmotic pressure which helps to maintain a normal blood volume and a normal water content in the interstitial fluid and the tissues.
Albumin content is most important in regulation of colloidal osmotic or oncotic pressure.
Decrease in albumin level results in loss of water from blood and its entry into interstitial fluids causing edema.
CATALYTIC FUNCTION (enzymes):
e.g lipases for removal of lipids from the blood

11. FUNCTIONS OF PLASMA PROTEINS (cont.)
PROTECTIVE FUNCTION:
Immunoglobulins combine with foreign antigens and remove them.
Complement system removes cellular antigens.
Enzyme inhibitors remove enzymes by forming complexes with them. e.g. a1-antitrypsin combines with elastase, trypsin and protects the hydrolytic damage of tissues such as lungs.
Some proteins increase during acute phase and protect the body. E.g. a1-antitrypsin, a2-macroglobulins.

12. FUNCTIONS OF PLASMA PROTEINS (cont.)
BLOOD CLOTTING:
Many factors are involved in clotting mechanism and prevent loss of excessive amount of blood; e.g. clotting factors IX, VIII, thrombin, fibrinogen etc.
An excess of deficiency leads to a disease; e.g. hemophilia, thrombus formation
ANTICOAGULANT ACTIVITY (thrombolysis):
Plasmin breaks down thrombin and dissolves the clot
BUFFERING CAPACITY:
Proteins in plasma help to maintain acid-base balance

13. PLASMA PROTEINS AS ANTIOXIDANTS
Transferrin
Ferritin
Ceruloplasmin
Haptoglobin
Hemopexin (binds heme and transfers it to the liver)
act as antioxidants:
remove Fe 2+ and thus prevent the Fenton reaction:
H2O2 + Fe2+ → HO• + OH− + Fe3+

14. Measurement of Plasma Proteins
A) Quantitative measurement of a specific protein:
Chemical or immunological reactions
B) Semiquantitative measurement by electrophoresis:
Proteins are separated by their electrical charge in electrophoresis
Five separate bands of proteins are observed
These bands change in disease