For All Medical & Non Medical Students

1. Plasma Proteins
GLOBULINS
By
N.Santhosh Kumar
Asst.Professor
Department of Biochemistry
SIMS & RH

2. • Globulins is a glycoprotein with mol wt – 90 to 1300kDa.
• There are separated by half saturation with ammonium sulphate.
• Main functions: Transport &Immunity.
• Globulins contributes different fractions in electrophoresis (α1,α2,β, γ
-globulins).
• Normal range of Globulins -1.8 to 3.6 gm%

3. Fraction Examples c (gm%)
1-globulins 1-antitrypsin, 1-acid glyco- protein, RBP,
1-lipoprotein (HDL), 1-fetoprotein, 0.1 to 0.4
2-globulins Haptoglobin, Ceruloplasmin
2-Macroglobulin, Thyroxin-binding
globulin (TBG),
0.4 to 0. 8
-globulins C-reactive protein (CRP) Transferrin,
Hemopexin, 2-Micro globulin, -lipoprotein
(LDL)
0.5 to 1.2
-globulins IgG, IgA, IgM, IgE, IgD, 0.7 to 1.5

4. α1 –antitrypsin (AAT) / α1-protease inhibitor
Glycoprotein(mol wt – 54kDa), synthesized by liver

5. AAT Inhibits activity of enzyme elastease – degrades elastin
protein (elasticity to the lungs)
AAT deficiency is an inherited disorder causes lung disease
(emphysema)& liver disease (neonatal hepatitis)

6. Emphysema (Abnormal distension of lungs by air)
Chronic obstructive lung disease, characterized by alveolar
damage

7. Enlarged alveoli
Compressed
alveoli duct
Collapsed
alveoli sac
Causes shortness of breath due to increasing of air sacs in the
alveolar, leading to difficulty in breathing

8. In chronic smoking

9. α1-feto globulin
• High conc. in foetal blood during mid pregnancy.
• Immunoregulatory during pregnancy
• Normal adult blood has less than 1 μg/100ml
• Increased in pregnancy, open neural tube defect (congenital
abnormalities caused by failure of the neural tube) Hepatoma
(cancer of liver)
• Decreased in Down’s syndrome (form of mental subnormality due
to a chromosome defect)

10. α2-macro globulin
 large plasma glycoprotein, synthesized by Monocytes, Hepatocytes &
macrophages with mol wt 7,20,000.
Functions:
 Carries of many growth factors such as platelet derived growth factor.
 Inactivates all the proteases – invivo Anticoagulant.
 Natural inhibitor of endopeptidase such as trypsin, plasmin, chymotrypsin
& thrombin etc.

11. Clinical significance:
Normal serum level – 130 – 300 mg/dl.
 Increased levels - Nephritic syndrome, cirrhosis
Collagen disorders
 Decreased levels - myeloma, Pancreatitis, Peptic ulcer

12. Haptoglobin (α2 globulin)
 syn in liver with half life is 5days.
 It binds and clears the free Hb found outside of RBCs from circulation.
Hb-Hp half life is 90min.
 Helps in the breakdown of Hb to bilirubin.
 Prevents the loss of iron in the urine

13. Clinical significance :
Levels in serum 40-170mg/dl
 Increased in Inflammatory conditions
Rheumatic diseases.
 Decreased: intravascular haemolytic anemia
- Hp assay is used to screen & monitor intravascular haemolytic
anaemia

14. Ceruloplasmin
 It is a blue colored α2-globulin, syn in liver .
 Major transport protein for copper (6 - 8 cu atoms /mol).
 Shows ferroxidase activity (helps in oxidation of Fe2+ to Fe3+.
Clinical significance :
Normal levels – 25 -50 mg/dl

15. Increased levels
Inflammatory conditions
Collagen disorders
Decreased levels
Wilson's disease,
Malnutrition
Nephrotic syndrome

16. C - reactive proteins
 It is a β-fraction of globulin with 115-140 KD & binds
to T- lymphocytes.
 CRP was discovered in serum of pneumococcal
pneumonia patients.
 CRP reacts with C-polysaccharides of Capsule of
pneumococci bacteria.
 Stimulated complement activity, Phagocytosis by
macrophages - clears necrotic cells , apoptotic cells
and bacteria.

17.  Useful in differentiating bacterial from viral infections. because CRP levels
increased in bacterial infections only

18. γ- globulins
 γ- fraction of globulins are
immunoglobulin / antibodies.
 Produced by plasma cells
 Igs provide resistance because
they can neutralize toxins &
viruses, Opsonize microbes,
Activate complement & prevent
the attachment of microbes to
mucosal surfaces

19. Types and functions of Immunoglobulins
Igs Structure /
Characteristics
Found in Total %
in Ig
Functions
IgG Exists as simple Y shaped
structure. Can cross the
placental barrier.
Blood,
lymph fluid
& CSF
85% -Involved in precipitation, complement
fixation reactions & neutralization of
toxin compounds.
IgA Exists as dimer joined by a
J chain
Saliva,
tears, sweat
10-13% - Protects the body surface from foreign
substance.
IgM Largest antibody exists as
pentamer held together by J
chain. Primary antibody
and acts as first line
defense
Body fluids 5-10% - Protects against invading micro-
organisms.
- Promotes the phagocytosis,
agglutination, bacteriolysis reactions.

20. Igs Structure / Characteristics Found in Total %
in Ig
Functions
IgM Largest antibody exists as
pentamer held together by J
chain. Primary antibody and
acts as first line defense
Body fluids 5-10% - Protects against invading micro-
organisms.
- Promotes the phagocytosis,
agglutination, bacteriolysis reactions.
IgE Exists as simple Y shaped
structure
Lungs, skin,
& mucous
membrane
5% - Receptor for allergens & parasitic
antigens.
- Protection against parasitic infections.
- Responsible for anaphylactic
hypersensitivity.
IgD Exists as simple Y shaped
structure
Body fluids 1% Serve as recognition of receptors for
antigen.

21. Acute phase proteins
&
Acute phase reactants (APRs)

22. Def:
levels of certain proteins in plasma increases (or) decreases
during acute inflammatory states (or) secondary to certain types of
tissue damage.
 APRs concentration changes in:
 infection
 surgery
 injury
 cancer

23. acute inflammatory
states

24. Mechanism of AFPs

25. TYPES OF ACUTE PHASE PROTEINS
Positive A.P.P
• 1-antitrypsin
• α2- macroglobulin
• C-reactive protein (CRP)
• Haptoglobin (HP)
• Ceruloplasmin
Liver disease, trauma, burns
Nephritic syndrome, collagen
disorders
Inflammatory conditions,
malignancies, collagen disorders
Hepatocellular damage
&nephrotic syndrome.
Myocardial infarction,
inflammations, trauma
&stress

26. Negative A.P.P
• Albumin
• Transthyretin/TBP
•Transferrin
Inflammation, liver diseases,
nephrotic syndrome
malnutrition
Inflammation, malignancy,
nephrotic syndrome
Liver diseases, thyrotoxicosis,
malnutrition
TYPES OFACUTE PHASE PROTEINS

27. TRANSPORT PROTEINS

28. Transport Proteins Transports
Pre albumin / transthyretin
(Thyroxine binding prealbumin
Thyroid hormones of thyroxin,
Retinol, steroid hormones
Albumin Bilirubin, Free fatty acids, Calcium,
Drugs etc
Retinol binding protein Vitamin - A (retinol).
Thyroid binding globulin Thyroid hormones
Haptoglobin Hemoglobin
Transferrin Iron (Ferrous state)
HDL Carries cholesterol from peripheral
tissues to liver
LDL Carries cholesterol from liver to
peripheral tissues.

29. Case base Question
Patient gives history of cough, fever since 1 month and dyspnea
(difficulty in breathing) since 4 days. Family history reveals that
one of his brother had died earlier due to lung disease
Q a) What could be the probable diagnosis?
b) What is the biochemical defect?
c) Explain this with respect to chronic smoking?

30. Separation Of Plasma Proteins
Electrophoresis
Based on the migration of charged solutes of a solution towards the opposite
electrical poles in an electric field.

31. Multiple myeloma
M-band between beta and gamma region.
Q) a) What is the probable diagnosis?
b) Mention the biochemical defect

32. Chronic infection,
broad based increase in gamma region; general increase in alpha-1 and alpha-2
bands; decreased albumin band

33. Nephrotic syndrome
hypoalbuminemia; prominent alpha-2 band

34. Cirrhosis of liver;
γ-β- bridge observed (increased γ & β- globulins) &
decreased albumin band

35. Agammaglobulinemia ;
Absent or decreased γ globulins observed
& other bands are normal

36. Q) a) What is the probable diagnosis?
b) Mention the biochemical defect.

37. Next PPT on
PP-03: Gamma globulins (Immunoglobulins) &
Multiple Myeloma
N.Santhosh Kumar /Asst.Professor of Biochem / SIMSRH

38. Thank you
The End