Plasma Proteins- Definition, Classification, Properties, Functions

Plasma proteins also known as serum proteins or blood proteins are made up of simple and conjugated proteins. Their average concentration in plasma is not fixed and is affected by the presence of protein but usually, it is 7.4% and varies from 6.5% and 8.4% in the healthy individual. So, using their concentration as the criteria, they can be used in disease diagnosis and prognostic.

Plasma Protein
Plasma Protein

Classification of plasma proteins

1. Albumin

2. Globulin 

  • Alpha 1 globulin
    • Alpha 1: acid glycoprotein
    • Alpha 1 fetoglobulin
    • Alpha 1 antitrypsin
  • Alpha 2 globulin
    • Ceruloplasmin
    • Haptoglobin
  • Beta globulin
    • Transferrin
    • C- reactive protein
    • Hemopexin

3. Other important plasma

  • Bence-jones protein
  • Fibrinogen

1. Albumin

Albumin Characteristics

  • The globular protein is made up of a single polypeptide chain and has 610 amino acids.
  • Molecular weight: 69,000
  • Comprise 60-70% of plasma protein
  • Isoelectric PH: 4.7
  • Synthesized in liver
  • Full saturation of ammonium sulfate is required for its precipitation.
  • 3.5 to 5.5 g% is its normal serum concentration in a healthy adult.

Albumin Functions

  • 70-80% of the total colloidal osmotic pressure in the vessel is maintained by albumin, which is a macromolecular organic compound and out of the 25-30 mm Hg COP range,  albumin alone contributes to the 22 mm Hg COP range.
  • To draw the water inside the plasma from interstitial fluid, an outside force is required known as colloidal osmotic pressure or oncotic pressure, which maintains the water concentration in the plasma. So albumin helps in building that pressure.
  • It also helps in calcium ions, unconjugated bilirubin, thyroid hormones, and nonesterified fatty acid transportation into the plasma. 
  • Acidic and neutral drugs such as warfarin sodium, diazepam, furosemide, acetylsalicylic acid, and penicillin are transported using albumin.

Albumin Clinical significances

  • When the serum albumin concentration becomes lower than 2.5g% then it leads to the formation of edema in the body, due to which the fluid start migrating from the vascular compartment to the interstitial spaces. Liver disease, glomerulonephritis, and protein-energy malnutrition are some diseases that form due to the lower concentration of serum albumin. 

2. Globulin

Globulin Characteristics

  • Globular protein
  • Water-insoluble
  • Molecular weight: 90,000- 1,300,000
  • Electrophoresis is used to differentiate it into alpha, beta, and gamma globulin.

a. Alpha 1 globulin

i. Alpha 1: Acid glycoprotein

Characteristics

  • Aka orosomucoid protein
  • 60-140mg/ 100 ml= normal serum concentration
  • Site of synthesis: liver

Clinical significance

  • Progesterone is a steroidal hormone that is transported using acid glycoprotein. 
  • Aka acute phase protein because it acts as a biomarker for acute inflammation.
  • Carry drugs such as morphine, propranolol, quinidine, etc.

ii. Alpha 1- Fetoglobulin

Characteristics

  • Found in pregnant women in fetal blood circulation
  • Concentration in healthy individual: <1 microgram/ 100mL.

Clinical significance

  • Hepatocarcinoma can be detected using fetoglobulin

iii. Alpha 1- antitrypsin

Characteristics

  • The activity of protease can be inhibited by using antitrypsin as a serum trypsin inhibitor. 
  • Concentration: 200-400 mg/100ml in adults.
  • Place of synthesis: liver
  • During small injury, hepatocellular carcinoma, malignancy, burns, and liver cirrhosis, the concentration of antitrypsin increases and thus is an important acute phase reactant protein. 
  • Neutrophils secrete antitrypsin and also secrete from the enzyme that degrades elastin protein in lung and liver tissues. 

Clinical significance

Lung disease: The presence of defective alleles like “PiM, PiF, and PiZ, can cause a genetic disorder known as alpha 1- antitrypsin deficiency.

Obstructive pulmonary diseases and liver cirrhosis is common in people with the ZZ genotype.

Emphysema and COPD are most likely to occur in ZZ genotype people with a smoking habit because the smoke causes the oxidation of 358 methionine residing in antitrypsin and makes it inactive.

Diagnostic tool: malignancy of gonads can be diagnosed using antitrypsin.

Liver cirrhosis: juvenile liver cirrhosis is a result of an antitrypsin deficiency.

b. Alpha 2 globulin

i. Ceruloplasmin

Characteristics

  • Type of glycoprotein which has cofactor such an eight copper atoms
  • Serum concentration: 30mg/100ml
  • Place of synthesis: liver
  • 90% of total serum copper is present in ceruloplasmin.

Clinical significance

  • Conversion of a ferrous ion into a ferric ion is done with this, thus it is an important ferroxidase enzyme. 
  • A decrease in serum concentration is the marker for liver disease and mineral deficiency.
  • An autosomal recessive trait of Wilson’s disease is an accumulation of copper in the liver and brain tissues. Symptoms include edema of the legs and abdomen, emotional disturbance, behavior change, anxiety, and skin discoloration.
  • Another X-linked recessive trait is the deficiency of copper in the body in Menkes disease. Symptoms include weakness in the muscle, deficiency in growth, brain damage, seizures, brittle hairs, etc. usually seen in babies and result in mortality after 2-3 years of birth.  

ii. Hemoglobin

Characteristics

  • Formed from the covalently joining of two light chains or alpha chains and two heavy chains or beta chains by disulfide bridges.
  • Place of synthesis: liver
  • Serum concentration: 30-200mg/100 mL.

Clinical significance

  • Hemoglobin is the release from RBC when it undergoes lysis as a common even in a healthy individual. 
  • Free heme that contains ferrous ion undergoes a series of reactions known as Fenton reaction that generates ROS and can damage protein, DNA, and lipid layer and become toxic to tissues of loos vessels.
  • Haptoglobin-hemoglobin complex is formed when free hemoglobin binds to haptoglobin using an alpha chain and it can pass through the glomerular filter.
  • Loss of free hemoglobin in urine is thus prevented by haptoglobin.
  • Free hemoglobin went through biodegradation when the haptoglobin-hemoglobin complex is taken up by macrophages and the spleen.
  • Cytoprotective and antioxidant functions are performed by haptoglobin.
  • An increase in its level during acute inflammation and infection makes it an acute-phase protein.
  • Hemolytic anemia can be detected using haptoglobin as its concentration decrease in hemolytic anemia. 

c. Beta- globulin

i. Transferring

Characteristics

  • It is a glycoprotein that contains iron
  • Place of synthesis: liver
  • Concentration in serum: 200-350 mg/100 mL
  • “apo-transferrin is a single polypeptide chain which when binds with 2 ferric ions form “transferrin”

Clinical significance

  • For biosynthesis of hemoglobin, it delivers iron to bone marrow and distributes it in a ferric state.
  • Provide innate immunity.
  • Iron deficient anemia can be detected using this, as its concentration increase in iron-deficient anemia.
  • During liver cirrhosis, protein-energy malnutrition, burns, acute infection, and glomerulonephritis, its concentration decrease which can be used as a biomarker.

ii. C-reactive protein

Characteristics

  • Beta globulin pentameric protein
  • Concentration: less than 1mg/100mL. increase in its concentration is seen during aging, pregnancy, burns, and inflammation
  • Place of synthesis: liver
  • It derived its name from its interaction with group C antigenic polysaccharides found in pneumococci.
  • The plasma membrane of dead cells and bacteria contains phosphocholine which reacts with C-reactive protein and forms a complex which can activate the complement system, which in turn activates macrophages and T lymphocytes.

Clinical significance

  • It can act as a non–specific biomarker for infection and inflammation as it is an acute-phase-reactive protein and thus, its serum concentration increases in the presence of acute infection or inflammation.
  • It can better perform as a biomarker for inflammation than erythrocyte sedimentation rate.

iii. Hemopexin

Characteristic

  • Beta globulin formed from a single polypeptide chain
  • Place of synthesis: liver
  • Serum concentration: 50-100mg/100 Ml in adults. It is low in infants and becomes normal after the first birth year.
  • Strongly bind with “heme” in a 1:1 ratio.
  • Properties such as cytoprotection and antioxidation are found in this which is similar to haptoglobin.

Clinical significance

  • During hemolytic anemia, its concentration decreases which can use for diagnosis.

3. Other important plasma proteins

a. Bence-jones protein

Characteristics

  • During malignancy, an antibody is formed from a rapid division of monoclonal plasma cells known as paraprotein, thus bence-jones protein is a type of paraprotein.
  • Molecular weight: 45,000
  •  Formed from light chain either kappa or lambda abnormal immunoglobulin
  • Contain 217 amino acids.

Clinical significance

  • Tumor plasma such as multiple myeloma contains bence-jones protein in its blood and urine.
  • Diagnosis of multiple myeloma uses a concentration of serum paraprotein which is 3mg/10 ml as a diagnostic measure.
  • This protein precipitate at 60 degree Celsius in urine. Heating at a temperature higher than that causes the precipitate to dissolve and when colled again, ppt reappears.

b. Fibrinogen

Characteristics

  • Aka clotting factor is a soluble plasma protein
  • It is inactivated form of fibrin that is required for blood clotting.
  • Place of synthesis: liver
  • Serum concentration: 200-400 mg/100mL 
  • Molecular weight: 350,000-450,000.

Clinical significance

  • Blood clotting factor
  • In liver disease, its concentration decreases
  • High bleeding can also be diagnosed due to its low concentration
  • Acute-phase protein

Functions of plasma proteins

  1. Acid-base regulation: plasma protein being amphoteric can act as a buffer to maintain the balance between the acid-base of blood and other bodily fluids.
  2. Colloidal osmotic pressure: aka oncotic pressure is maintained by plasma proteins, which are essential for the distribution of water in blood vessels and interstitial spaces. 
  3. Blood clotting: plasma proteins such as fibrinogen, prothrombin, and other blood clotting factors are present in an inactive form in plasma. During the injury, they got activated and help in blood clotting.
  4. Provide immunity: B lymphocytes form immunoglobulins which are present in plasma and provide immunity against pathogens
  5. Help in the transport of substance: transport of large molecules from the blood to tissue is carried out by albumin and globulins. 
  6. Provide nutrition: plasma protein is a simple protein that contains amino acid and thus provide nutrition.
  7. Maintain viscosity in blood: the presence of globulins and fibrinogens in plasma helps in maintaining the viscosity of blood, which is important for maintaining normal blood pressure.
  8. Storage of enzymes: lipase, amylase, and transaminase are enzymes stored in plasma in small amounts. Changes in their concentration in plasma can be a biomarker for the disease.
  9. Reserve proteins: plasma proteins are converted to amino acids during fasting and carried to tissues by the circulation of blood and use to synthesize tissue protein.

References

  1. Gupta, A. (2018). Plasma Proteins. Comprehensive Biochemistry for Dentistry, 67–75. doi:10.1007/978-981-13-1035-5_4
  2. Alberti KGMN (ed) (1978) Recent advances in clinical biochemistry. Churchill Livingstone, London
  3. Baron DN (1982) A short textbook of chemical pathology, 4th edn. Wiley, New York Conn EE, Stump PK (1969) Outline of biochemistry, 2nd edn. Wiley, New Delhi
  4. https://biochemden.com/plasma-proteins/
  5. https://www.healthline.com/health/plasma-protein-tests
  6. https://byjus.com/questions/what-is-the-importance-of-plasma-proteins/
  7. https://www.biologydiscussion.com/blood/plasma-proteins/plasma-proteins-origin-and-functions-blood-humans-biology/81204
  8. https://www.slideshare.net/namarta28/plasma-proteins
  9. https://www.euroformhealthcare.biz/medical-physiology/functional-roles-of-the-plasma-proteins.html

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