This document summarizes plasma proteins. It describes that plasma is the liquid portion of blood that remains after clotting or centrifugation. The major plasma proteins are albumin, globulins, and fibrinogen. Albumin is synthesized in the liver and serves important transport and homeostatic functions, while globulins include acute phase proteins and immunoglobulins. Several specific plasma proteins are also discussed in detail, including their structure, function, clinical significance, and role in conditions like Wilson's disease.
2. Total blood volume is about 4.5 to 5 litres in adult human beings.
If the blood is mixed with an anticoagulent and centrifuged, the cell
components (WBC and RBC) are precipitated.
The supernatant is called plasma.
If blood is withdrawn without anticoagulant and allowed to clot,
after two hours liquid portion is separated from the clot.
This difrinated plasma is called serum.
Total protein content of normal plasma is 6 – 8 g/dl.
The plasma protein consist of albumin (3.5 to 5 g/dl ), globulins (
2.5 to 3.5 g/dl ) and fibrinogen (200- 400mg/dl ).
The albumin:globulin ratio is usually between 1.2:1 to 1.5 :1.
Almost all plasma proteins, except immunoglobulins are
synthesized in liver.
3. concentration 65 –80 g l
simple or conjugated (glycoproteins, lipoproteins)
separation:
a) salting-out methods albumin, globulins, fibrinogen
b) electrophoresis albumin, globulin 1, 2, , fractions:
-
+
2
1
albumin
5. Plasma proteins participate in:
1. blood coagulation
2. maintenance of homeostasis (pH, osmotic pressure)
3. defence against infection
4. transport of
metabolites
hormones metabolic waste
nutrients
drugs
6. 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…)
7. Acute phase reactants (APRs)
Their levels change during acute inflammatory response
APRs concentration changes in:
infection
surgery
injury
cancer
9. ALBUMIN
The normal range of albumin is 3.5 – 5 g/dl
60% of the total plasma protein
Human albumin has a molecular weight of 69,000 and consists of a
single polypeptide chain of 585 amino acids with 17 disulfide bonds.
Albumin is exclusively synthesized by the liver.
Liver produces about 12 g albumin per day.
Albumin has an half – life of 20 days.
Functions: maintenance of the osmotic pressure of plasma
transport of:
steroid hormones, free fatty acids, bilirubin, drugs,
(sulfonamides, aspirin), Ca2+, , Cu2+
10. Clinical Significance of Albumin:
1.Albumin, binding to certain compounds in the plasma, prevents them
from crossing the blood-brain barrier e.g. albumin- bilirubin complex,
albumin-free fatty acid complex.
Hypo-albuminemia:
Decreased plasma albumin level is observed in
1.Cirrhosis of Liver: Synthesis is decreased.
2.Malnutrition: Availability of amino acids is reduced and so albumin
synthesis is affected.
3.Nephrotic syndrome: Permeability of kidney glomerular membrane is
defective, so that albumin is excreted in large quantities.
4. Albuminuria: Presence of albumin in urine is called as albuminuria.
It is always pathological.
11. Large quantities of albumin is lost in urine in nephrotic syndrome.
Small quantities are lost in urine in acute nephrities, and other
inflammatory conditions of urinary tract.
In Microalbuminuria or minimal albuminuria or pauci-albuminuria,
small quantity of albumin is seen in urine.
5.Protein losing enteropathy: Large quantities of albumin is lost from
intestinal tract.
Albumin-Globulin Ratio:
In hypo-albuminemia, there will be a compensatory increase in
globulins which are synthesized by the reticulo-endothelial system.
Albumin-globulin ratio (A/G ratio ) is thus altered or even reversed.
Hyperalbuminemia: Increased concentration of plasma albumin is
called as hyperalbuminemia.
12. Hyperalbuminemia is rare and is seen in presence of acute dehydration
or shock.
An increase in albumin concentration will only be temporary as
interstitial water is drawn into the vascular bed by increased osmotic
forces.
Hypoproteinemia:
Since albumin is the major protein present in the blood,any condition
causing lowering of albumin will lead to reduced total proteins in blood
( hypoproteinemia ).
Hyper-gamma-globulinemias:
1.Low albumin levels: When albumin level is decreased, body tries to
compensate by increasing the production of globulins from
reticuloendothelial system.
13. 2.Chronic infections: Gamma globulins are increased .
3.Multiple myeloma: Drastic decreased in globulins are seen in para-
protenimias, when a sharp spike is noted in electrophoresis.
This is termed as M-band.
The monoclonal origin of immunoglobulins are seen in multiple
myeloma.
Globulins
Globulins constitute several proteins that are separated into 4
distinct bands (α1, α2, β and γ – globulins ) on electrophoresis.
Globulins ( α and β) are synthesized in the liver.
γ – globulins are synthesized by plasma cells and B-cells of
lymphoid tissue.
14. 1.α-Globulins: They are glycoproteins and are classified as α1 and α2
depending on their electrophoretic mobility.
1. α1 – acid glycoprotein: Also called as oroso-mucoid.
Its carbohydrate content is about 41%.
oroso-mucoid is considered to be a reliable indicator of acute
inflammation.
oroso-mucoid binds the hormone progesterone and function as a
transport protein for this hormone.
Clinical Importance:
Increase: Acute and chronic inflammatory diseases, cirrhosis of liver
and malignant conditions.
Decrease: Low concentrations occurs in generalised
hypoproteinaemic conditions, hepatic diseases,
malnutrition,nephrotic syndrome.
15. 2. α1-fetoprotein:
It is present in high concentration in foetal blood during mid
prignency.
Normal adult blood has <100 μg/dl.
It may increase during pregnancy.
Clinical Importance:
Useful in determining the hepatocellular carcinoma ( tumour marker )
16. 1- ANTITRYPSIN
(1-antiproteinase)
Synthesized by hepatocytes and macrophages
Major component (90 %) of the 1-fraction
Glycoprotein, highly polymorphic
Function: principal plasma inhibitor of serine protease (inhibits
trypsin, elastase)
deficiency has a role in emphysema – proteolytic damage of the
lung methionine involved in AT binding to proteases is oxidized by
smoking AT no longer inhibits proteases increased
proteolytic damage of the lung, particularly devastating in patients
with AT-deficiency
Effect of smoking on 1- AT: The amino acid methionine at position
358 of 1- AT is involved in binding with proteases.
17. Smoking causes oxidation of this methionine to methionine
sulfoxide. As a result, 1- AT with methionine sulfoxide cannot
bind and inactivate proteases.
Emphysema is more commonly associated with heavy
smoking .
1- AT deficiency and liver diseases: This is due to the accumulation
of a mutant 1- AT which aggregates to form polymers, these
polymers cause liver damage (hepatitis) followed by accumulation of
collagen resulting in fibrosis ( cirrosos).
1- AT has been used a tumour marker , it is increased in germ cell
tumours of testes and overy.
18. Α2- Globulins:
1.Ceruloplasmin: Also called as Ferroxidase, an enzyme which helps in
the incorporation of iron into transferrin.
It is a copper containing α2 – Globulin, a glycoprotein with enzyme
activities.
It is synthesized in liver, where 6 to 8 copper atoms are attached to a
protein, apoceruloplasmin.
Conc. in plasma: 300 mgl
Functions: Carries 90% of copper in plasma (copper – cofactor for a
variety of enzymes);
1 molecule binds 6 atoms of copper;
binds copper more tightly than albumin that carries other 10%
of copper albumin may be more important in copper
transport (donates copper to tissues more readily)
19. Causes of ceruloplasmin decrease:
Liver diseases, in particular Wilson´s disease:
genetic disease in which copper fails to be excreted into the bile
and accumulates in liver, brain, kidney, and red blood cells
cause: mutations in the gene encoding for copper-binding
ATPase
consequences:
1. accumulation of copper in liver, brain, kidneys… liver
disease, neurologic symptoms
2. ↓ coupling of copper to apoceruloplasmin low plasma
levels of ceruloplasmin
Causes of ceruloplasmin increase:
Inflammatory states
Carcinomas, leukaemia
Rheumatoid arthritis
20. Wilsons disease:
Normal blood level of ceruloplasmin is 25-50mg/dl. This level is
reduced to less than 20 mg/dl in Wilsons hepatolenticular
degeneration.
It is an inherited autosomal recessive condition, the incidence of the
disease is 1 in 50,000.
The basic defect is a mutation in a gene encoding a copper binding
ATPase in cells, which is required for copper excretion from cells. So,
copper is not excreted through bile, and hence copper toxicity.
Increased copper content in hepatocytes inhibits the incorporation of
copper to apo-ceruloplasmin. So ceruloplasmin level in blood is
decreased.
Clinical Features:
Accumulation in liver leads to hepatocellular degenaration and
cirrhosis.
21. Deposits in brain basal ganglia leads to lenticular degenaration and
neurological symptoms.
Copper deposits as green or golden pigmented ring around cornea;
this is called Kayser-Fleischer ring.
Treatment consists of a diet containing low copper and injection of D-
penicillamine, which excretes copper through urine. Zinc decreases
copper absorption, Zinc is useful in therapy.
α2 – Macroglobulin:
It is a high molecular weight protein ( 8,00,000 ) and is major fraction
of α2 – fraction.
α2 – macroglobulin inhibits protease activity and serves as an
anticoagulant.
Its concentration in plasma is elevated in nephrotic syndrome
Synthesis: Synthesized in hepatocytes.
Normal range is 130-300mg/dl.
22. 2.Haptoglobin: Haptoglobin is plasma glycoprotein with an
approximate molecular weight of 90,000.
Hp is an acute phase protein.
It is composed of two alpha-chains and only one beta-chain.
Site of formation: It is synthesized in liver by hepatocytes and to a very
small extent, in cells of R.E.cells.
Functions of haptoglobin:
Haptoglobin binds with the free hemoglobin ( known asextra-
corpuscular hemoglobin ) that spills into the plasma due to hemolysis.
The haptoglobin-hemoglobin ( Hp-Hb ) complex cannot pass through
the glomeruli of kidney while free Hb can, Haptoglobin, therefore,
prevents the loss of free Hb into kidney.
23. Clinical significance:
Hemolytic anemia is associated with decreased plasma concentration
of haptoglobin.
The half-life of Hp is about 5 days while that of Hp-HB complex is 90
mints.
In hemolytic anemia, free Hb in plasma is elevated leading to increased
formation of Hp-Hb complex.
This complex, is rapidly cleared from the plasma resulting in
decreased Hp levels.
β- globulins:
1.Transferrin:
It is a non- heme iron-containing protein.
It is glycoprotein, with molecular weight 70,000 approximately.
Protein part is, apo-transferrin, a single chain polypeptide and can bind
24. Two atoms of Fe to form transferrin.
Its concentration in plasma is 3 g/l.
Functions:
Transport iron : from catabolism of heme and from food to the sites
where the iron is required.i.e., to the bone marrow and other organs.
2 moles of Fe3+ per 1 mol of transferrin.
Site of synthesis:
Synthesized from Liver.
Clinical Importance:
Increase: Serum transferrin levels are increased in Iron deficiency
anemia and in last months of pregnency.
Decrease: Protein calorie malnutrition, cirrhosis of liver, Nephrotic
syndrome, myocardial infarction, malignencies.
25. Receptor-mediated transferrin endocytosis
Ferro-transferrin binds to the
receptors on the cell surface → the
complex is internalized into an
endosome
In endosomes, iron dissociates
from trans-ferrin (enabled by low
pH & Fe3+ Fe2+ reduction) and
enters cytoplasm
Iron is delivered to intracellular
sites or bound to ferritin (Fe2+
Fe3+ oxidation and Fe3+ storage)
Apotransferrin, associated with the
receptor, returns to the membrane,
dissociates from the receptor and
re-enters plasma.
26. Acute phase proteins:
The level of certain proteins in blood may increase 50 to 1000 folds in
various inflammatory and neoplastic conditions, Such proteins are
acute phase proteins.
1. C-reactive protein
CRP is a major component of acute phase proteins.
It is produced in the liver and its concentration is <1 mg/dl.( C-stands
for carbohydrate to which it binds on capsule of pneumococi ).
CRP is a beta – globulin and has a molecular weight of 115 – 140 kD.
It can stimulate complement activity and macrophage phogocytosis.
CRP level, especially high sensitivity CRP level in blood has a positive
correlation in predicting the risk of coronary artery diseases.
27. 2.Ceruloplasmin
3. Alpha 1 – antitrypsin
4. Alpha 2 – macroglobulin
Negative Acute Phase Proteins
During an inflammatory response, some proteins are seen to be
decreased in blood, those are called as negative acute phase proteins.
E.g., Albumin, pre-albumin ( transthyretin ), retinol-binding protein and
transferrin.
Transport proteins:
1. Albumin: It is an important transport protein.
It transport of bilirubin, free fatty acids, calcium and drugs.
2. Pre- albumin: It is so named because of its faster mobility in
elecrophoresis than albumin.
It carries T3 and T4, So called as an transthyretin.
28. 3.Retinol-binding protein: It carries vitamin A. It is low molecular
weight protein, and so is liable to be lost in urine .
To prevent this lost RBP is attached with pre-albumin; the complex is
big and will not pass through kidney glomeruli.
Normal range is 3-6 mg/dl.
4.Thyroxine Binding Globulin ( TBG) :
It is the specific carrier molecule for thyroxine and tri-iodothyronine.
TBG level is increased in pregnancy; but decreased in nephrotic
syndrome.
5. Transcortin:
It is also known as Cortisol binding globulin ( CBG ).
It is the transport protein for cortisol and corticosterone.
6. Haptoglobin.
29. IgG is the predominant immunoglobulin in blood, lymph, peritoneal
fluid, and cerebrospinal fluid.
Collectively, it makes up more than 75% of serum immunoglobulin
and is synthesized at a high rate (over 30 mg/kg/d, second only to
IgA).The presence of high-affinity IgG is the hallmark of secondary
humoral immune responses
The selection of IgG subclass by a particular immune response
does not appear to be random: in murine systems, anti-
carbohydrate specificities tend to be IgG3, anti-protein IgG1, and
anti-viral IgG2a.
In man, reactivities against polysaccharide immunogens are
skewed toward IgG1 and IgG2, while anti-protein and anti-viral
antibodies are biased in the direction of IgG1, IgG3, and IgG4.
