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In this article we will discuss about:- 1. Origin of Plasma Proteins 2. Functions of Plasma Proteins 3. Varieties 4. Chemistry 5. Separation 6. Rate of Regeneration 7. Relation of Diet.
Contents:
- Origin of Plasma Proteins
- Functions of Plasma Proteins
- Varieties of Plasma Proteins
- Chemistry of Plasma Proteins
- Separation of Plasma Proteins
- Rate of Regeneration of Plasma Proteins
- Relation of Diet to Plasma Proteins
1. Origin of Plasma Proteins:
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In the embryo, the primitive plasma and the plasma proteins are produced either by secretion or actual solution of the mesenchymal cells. The albumin fraction is the first to be formed. The other varieties appear later.
In the adults all the four fractions are produced by the liver. This is supported by isotopic experiments. Fibrinogen, prothrombin and albumin are manufactured only in the liver. Regarding globulin, several other sources have been suggested.
Such as:
(a) From the disintegrated blood cells,
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(b) From the reticulo-endothelial system (specially the y-globulin),
(c) From the tissue cells in general, and
(d) From lymphoid nodules.
The plasma proteins are not static entities. Isotopic experiments indicate that they are completely used up and replaced every fourteen days. Albumin synthesis is stimulated by osmotic pressure changes and by hypoproteinemia; globulin, by a depressed blood protein pool and fibrinogen by systemic inflammation.
2. Functions of Plasma Proteins:
1. Essential for Blood Clotting:
Fibrinogen and prothrombin are essential for coagulation of blood and take part in this process Fig. 4.2.
2. Maintain Colloidal Osmotic Pressure of Blood and Aid in Regulating the Distribution of Fluid between Blood and Tissue:
All the three proteins take part. Albumin having the smallest and the most symmetrical molecule exerts the maximum osmotic pressure. Osmotic pressure depends upon a number of molecules in the solution. Albumins have a considerably smaller molecular wt. than globulin and comprise 52 percent of plasma protein. One gram of albumin in 100ml will exert a pressure of 5.5 mm of Hg. Under the same conditions globulin exerts only 1.5 mm Hg. The total colloidal O.P. varies from 25 to 30 mm of Hg and albumin is responsible for 80% of it.
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3. Maintain Viscosity and Blood Pressure:
The proteins of plasma, mainly globulins due to larger molecules and asymmetry of their structure are responsible to some extent for the viscosity of blood, and viscosity is an important factor in maintaining blood pressure which is essential for efficient heart action. Whole blood is isoviscous with 25 percent albumin, 15 percent y-globulin and 2 percent fibrinogen. The relative viscosity of blood is 4.7 for men, 4.4 for women, 4.2 for children; that of plasma as 1.8 and that of serum as 1.5 relative to distilled water at 37° C. (98.6° F.).
4. Concerned with Erythrocyte Sedimentation Rate (ESR):
The plasma proteins exert a great influence upon the suspension stability of blood. This is chiefly dependent on fibrinogen, less on globulin and least on albumin. An increase in fibrinogen raises the sedimentation rate of red blood corpuscles by increasing the speed of rouleaux formation.
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Since, the plasma proteins alter in various diseases, determination of sedimentation rate is of considerable clinical importance and constitutes a guide to the progress of disease. It is determined by the methods of Wintrobe, Westergren and Cutler.
5. Act as Buffers:
They act as buffers in maintaining acid-base balance.
6. Act as a Protein Reserve:
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The plasma proteins serve as a storehouse of proteins from which the tissue can draw during starvation or inadequate protein diet.
7. CO2 Carriage:
Help CO2 carriage by forming carbamino proteins (vide CO2 carriage).
8. Form Trephones:
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The leucocytes prepare substances from the plasma proteins, called trephones, which are necessary for the nourishment of the tissue cells grown in culture.
9. Antibodies:
The antibodies being y-globulin in nature make up a small fraction of the globulins of plasma for defence against infection.
10. Help Transport of Certain Substances in Blood:
Plasma proteins combine with certain substances and help to carry them in the blood stream.
(a) Some hormones, enzymes, and clotting factors are part of globulin fraction of plasma proteins,
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(b) Iron (transferrin) and copper (ceruloplasmin) are bound to globulin fractions.
3. Varieties of Plasma Protein:
In normal individuals, total amount of plasma protein varies from 6.5 to 7.5% and average is about 7.0%.
It is made up of following varieties:
i. Serum albumin: 4.7 – 5.7%.
ii. Serum globulin: 1.3 – 2.5%.
iii. Fibrinogen: 0.2 – 0.4%.
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iv. Prothrombin.
v. Seromucoid (are also present).
Serum is the fluid part of blood after clotting. It contains only serum albumin and serum globulin. The albumin/ globulin (A/G) ratio is ordinarily 1.5 : 1.0. Different methods of separation indicate slightly different A/G ratio. Electrophoretic method of separation gives a ratio 1.2:1.0.
This ratio varies in different species but in the same species it remains almost constant in blood, lymph and serous transudations. In liver disease however due to diminished formation of albumin, the ratio may be reversed. Chemical analysis of the total serum proteins reveals that arginine/lysine ratio is 10 : 18. This ratio remains more constant than the albumin/globulin ratio.
Although it is customary to state that plasma contains several types of proteins yet it is highly probable that in the living animal all these different varieties remain combined together forming a single protein complex.
This complex is very loose and is easily broken down into different parts by addition of salts, alteration of pH, etc. The so-called serum albumin, serum globulin, fibrinogen, etc., are the parts of the same parent complex, isolated by different techniques of separation.
4. Chemistry of Plasma Protein:
Serum Albumin:
It constitutes the major part of the total plasma proteins. It is albumin in nature having a molecular weight, about 69,000. It is soluble in distilled water. Recent studies show that serum albumin is not a single pure entity.
It is a mixture of several albumins. It is precipitated by full saturation with ammonium sulphate. Isoelectric pH is 4.7. The albumin molecule is an ellipsoid, made up of a single polypeptide chain. It is smaller and more compact than other plasma proteins and is heat-coagulable.
Serum Globulin:
It is globulin in nature having a molecular weight, varying from 90,000 to 1,300,000. It is insoluble in distilled water, but soluble in salt solutions. It is coagulated at about 70° C. Globulin, like albumin, is also a mixture of several globulins.
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By means of Electrophoresis serum globulin has been separated into three fractions:
1. α1– and α2-Globulins- Mol. wt. ranges from 41,000 to 200,000, isoelectric pH 5.1. α1- Globulin consists of two Fractions- (a) one fraction combines with bilirubin, (b) another fraction helps in the carriage of lipids, steroids and glycoproteins, α2– globulin consists of α2-macroglobulins, mucoproteins, ceruloplasmin, hepatoglobulins—the latter combine with free haemoglobin in the plasma.
2. β-Globulin- Mol. wt. ranging from 90,000 to 1,300,000, isoelectric pH 5.6. β- globulins are- (a) β-lipoprotein which helps in the carriage of lipid, steroid and carotene, (b) Globulin which helps in the transport of iron, e.g., transferring (siderophilin) which can also combine loosely with cupric copper. Prothrombin is a β-globulin.
3. γ-Globulin- Mol wt. ranging grom 150,000 to 190,000 isoelectric pH 6.0.
By careful electrophoresis, several varieties of functionally different proteins have been isolated more or less in pure form from the globulin fraction. They are immune globulins, hypertensinogen, isohaemoagglutinins (α, β, αβ, etc., vide Blood Groups), prothrombin, plasma thromboplastins, certain anterior pituitary hormones, etc.
Fibrinogen:
It is globulin in nature, mol. wt. 341,000, and isoelectric pH 5.8. It is coagulated at about 56° C and precipitated by one-fifth saturation with ammonium sulphate and half saturation with NaCI. It is insoluble in distilled water. It is distinguished from other plasma proteins by its property of clotting, during which fibrinogen is converted into fibrin.
5. Separation of Plasma Protein:
The three proteins can be separated and isolated in the following way. Plasma is taken and its total protein is estimated by Kjeldal’s process. This includes all the three proteins. Then the total protein of serum from same sample is estimated. Since, serum contains only albumin and globulin, the difference between the two total protein estimations will give the amount of fibrinogen.
Another sample of serum is half saturated with ammonium sulphate. This will cause precipitation of all globulins. It is filtered. The filtrate which contains albumin is fully saturated with ammonium sulphate. Albumin will be precipitated. In this way the three fractions can be separated. [Other methods of separation are Electrophoresis, Isoelectric precipitation, Ultracentrifugation, Fractional separation by alcohol, etc.]
6. Rate of Regeneration of Plasma Proteins:
After depletion of plasma proteins, such as by severe haemorrhage or after blood donation, the plasma proteins come to the normal level in about fourteen days. Fibrinogen is regenerated first, then comes globulin and last of all serum albumin.
7. Relation of Diet to Plasma Proteins:
Whipple performed the experiment of plasmapheresis upon dogs. The dog was bled, and the cells were separated from plasma. The plasma was rejected and the cells were re-injected being suspended in Ringer- Locke’s solution. This is continued for several weeks after a protein concentration of 4% has been attained in order to exhaust the protein reserves.
Then it is found that on a standard diet, the rate of plasma protein regeneration is constant. It is seen that during fasting only 2 to 8 gm of plasma proteins are formed weekly by the body tissues. Regarding the efficacy of food protein, the more a particular protein resembles the plasma proteins in the quality and quantity of its amino acid content the more effective it will be in this respect.
Obviously, plasma itself will be the best. If whole plasma is given by mouth, for every 3 gm of plasma protein ingested, 1 gm of plasma protein is formed. The potency ratio is therefore 3:1. The potency ratio of the proteins in grains, potatoes, kidney or liver is 5: 1. That of red cell, heart or spleen is 10:1. From this, it is seen that excepting plasma proteins, a diet containing grains, potatoes, kidney or liver will regenerate the lost plasma proteins in the earliest time.
Moreover, it is found that plant and grain proteins favour globulin formation, whereas animal proteins favour albumin formation. Role of essential amino acids is note-worthy. Plasma proteins can be synthesized from amino acids if all the essential amino acids are freely supplied.
Methionine is essential for long continued production. Cystine is less effective and can replace methionine for short periods only. Vitamin K helps in the formation of prothrombin in the liver.
