PLASMA PROTEIN

Role of plasma proteins in “HUMAN”

An adult human have approximately 5.0L blood, it consists of plasma (55-60%) and blood cells (40-45%). Plasma is nothing but serum consisting clotting factor like fibrinogen while blood cells contains RBC (Erythrocytes), WBC (Leukocytes) and platelets(Thrombocytes). 

Mainly three plasma proteins are taken into count Albumin, Globulin, Fibrinogen. 

Globulin have four types which can be separated on the basis of their electrophoretic mobility and sedimentation coefficient, these are: α1-Globulin (α1-Fetoprotein, α1-Antitrypsin), α2-Globulin (α2-Macroglobulin, Haptoglobin),β-Globulin (Transferrin, Ceruloplasmin), γ-Globulin (Antibodies).

Albumin- Albumin is the major constitute of plasma proteins with a concentration 3.5-5.0g/dl. Liver is the organ from which it produces and around 12g albumin per day was produced by it. Albumin has a half-life 20 days.

Function:-

1) Osmotic function-Due to high concentration and low molecular weight it plays major role in maintaining osmotic pressure, falling of its level indicate ‘edema’ (accumulation fluids in tissue spaces).

2) Transport function- It binds with many biochemically important compound like fatty acid, bilirubin, steroid hormons, calcium and copper and transport them in circulation. Along with albumin other plasma protein also play role in this are prealbumin,retinol binding protein, thyroxin binding protein, transcortin and cortisol binding protein.

3) Nutritive and Buffering function- albumin serve as a source of amino acid for tissue protein synthesis and also have a little buffering action.

Purification from plasma: Cohn fractionation process is used to purify albumin from blood plasma. Albumin can separated based on pH, ethanol concentration, temperature, ionic strength.  

Globulin (globular protein) - Its molecular weight is higher than albumin and having a concentration 2.5 to 3.5g/dl. Different types of Globulin are:

α1 Antitrypsin - Having antiproteiase activity it combines with trypsin, elastase and other protease enzyme and inhibits their activity.

α1 Fetoprotein - However its role in human is unknown but in rodent it prevents the transport of estradiol across the placenta to the fetus thus its main function is to prevent the virilization of female fetuses.

α1 Macroglobulin - It inhibits the protease activity and serve as an anticoagulant.

Haptoglobin – It’s acute phase protein having highest binding affinity for hemoglobin and thus prevents the passing of Hb through glomeruli of kidney and play major role in nephrotic syndrome.

γGlobulin (Immunoglobulin - Ig/Antibodi) – Ig is a glycoprotein produces by plasma cells in response to an immunogen/foreign materials. Human have five Igs and all have ‘Y’ shaped structure with two identical heavy chain and two identical light chain. They are named on the basis of heavy chain which they contains like IgG (heavy chain γ, percentage 75-80% and monomer in structure having ability to cross placenta and transfer from mother to fetus.), IgA (heavy chain α, percentage 10-15%, dimer in structure and predominant in clostrum mainly found in secretion.), IgM (heavy chain μ, percentage 5-10%, pentamer and first antibody produces during an infection), IgE (heavy chain ε, percentage 0.002%, monomer in structure and tightly bound to mast cells and in response to allergen release histamine and causes allergy.), IgD (heavy chain δ, percentage 0.2%, monomer in structure and found on B cell surface and serve as B cell receptor.).

Fibrinogen – It is a glycoprotein produced by liver and having blood-clotting activity. Fibrinogen undergoes proteolytic cleavage catalyzed by thrombin to release small fibrinopeptides (A and B). This results in a formation of a fibrin monomers which can stick together to form hard clots.

Besides above major plasma protein others are:

Transferin - Transport iron to the circulation.

Ceruloplasmin – Ceruloplasmin transports copper to the circulation.

Transcortin – Transcortin transports cortisol and corticosterone to the circulation.

Retinol binding protein - Transports retinol to the circulation.

C-reactive protein – It involves in the promotion of immune system through the activation of complement cascade.

Clinical significance of plasma proteins

Hypoalbuminemia – Lower plasma albumin observed in malnutrition, nephrotic syndrome and cirrhosis of liver.

Emphysema - Emphysema is abnormal distension of lung by air around 5% of cases are due to deficiency of α1antitrypsin. Pneumonia and increase in the activity of macrophages releases elastase that damages lung tissues. In the normal circumstances, α1antitrypsin binds with methionine at 358 position of elatase and inhibits its action but due to smoking, this methionine oxidized to methionine sulfoxide and thus inhibit the action of α1antitrypsin.

Hepatitis – Accumulation of mutant α1antitrypsin by an unknown mechanism causes liver damage.

Hemolytic anemia – It is associated with decrease in plasma concentration of haptoglobin(Hp) as in hemolytic anemia free hemoglobin(Hb) level is increases result in formation of  Hp-Hb complex is high. Half-life of Hp is about 5 days and it is decreases to 90 minutes when it in forms of Hp-Hb complex.

Nephrotic syndrome – It is indicated by increase in α2Macroglobulin because in nephrotic syndrome majority of plasma proteins are lost by urine while α2Macroglobulin is retain due to its high molecular weight.

Multiple myeloma – It is associated with overproduction of abnormal immunoglobulins, mostly (75%) IgG and in some cases (25%) IgA or IgM.

Research point:
New anticoagulant protein JJ1 used for improvement of thrombosis treatment. JJ1 inhibits the catalytic activity of human alpha thrombin, inhibits thrombin catalyzed fibrin polymerization and platelet aggregation.