Significance of globulins

Presented by:Diksha CheetooRoll number 24

Plasma proteins

albumin Globulins fibrinogen

Alpha 1Alpha 2 Beta1Beta2

Gamma

Globulins can be separated by half saturation and by

electrophoresis.

Site of synthesis:α and β in liver

γ in plasma cells or B-cells of lymphoid tissue

α globulins

• They are glycoproteins• Further subclassified as

α1and α2

• Depending on their electrophoretic mobility

α1 globulins

• α1-acid glycoprotein• Also called orosomucoid• Considered to be a reliable

indicator of acute inflammation• Functions:• Binds to progesterone as a

transport protein for this hormone

• Carry needed carbohydrate to the site of tissue repair

Clinical importance

• Increase:• In acute inflammation, liver

cirrhosis and malignant conditions

• Decrease:• Hypoproteinemia, hepatic

diseases, malnutrition and nephrotic syndrome

α1 fetoprotein

• Also known as α1 fetoglobulin

• Present in high concentration in fetal blood during pregnancy

• The normal value is 1 mg/dl• Clinical importance• Tumour marker of hepato

cellular carcinoma

α1globulin inhibitor

Are the inhibitors of coagulationAlso inhibit digestive enzymes like

trypsin and chymotrypsin

α1 antitrypsin• Also known as α antiprotease • The protein is highly polymorphic,multiple

forms can be separated by electrophoresis• Synthesised in the liver and it is the

principle inhibitor of human plasma• It is a protease inhibitor.• It inhibits all serine proteases• E.g trypsin,

chymotripsin,plasmin,thrombin

• A very low or absence of α1globulin band in electrophoresis suggests α1antitrypsin deficiency

Phenotype:the homozygous phenotype Z

Z suffers from severe deficiency α1antitrysin and is susceptible to lung disease

and cirrhosis of liver

• Increase:• In response to inflammation. It is

considered as one of the “acute phase reactant”

• In trauma, burns, infarction, malignancy, liver disease.

inflammatory cells and red blood cells

• Chronic hepato cellular diseases and bilary obstruction

• In pregancy and also during contraception medication

• Neonates have serum concentration much higher than adults

• Decrease• Protein losing disorders:• Nephrotic syndrome and diffuse

hypoproteinemia• Emphysema of lungs• Juvenile cirrhosis of liver

Clinical significance

• Role in emphysema of lungs • About 5% of emphysema• Occurs mainly with ZZ phenotype• Normally α1 antitrypsin protects the

lungs from bacterial infection by binding with “active elastase”.

• When α1 antitrypsin is deficient the complex with elastase is not formed

• Active elastase brings about proteolysis of lung and tissue damage

elastase

• Absence of AAT

• Active elastase

• Lung tissue damage

• emphysema

• Presence of AAT

• Inactive elastase

• No lung tissue damage

• Role in smoking• Smoking oxidises the methionine of α1

antitrypsin • Inactivates the protein• It cannot bind with active elastase • Proteolysis of lungs and tissue damage

occurs• Accelerating development of emphysema

• Role in cirrhosis• Zz phenotype accumulate in the cisternae

or endoplasmic reticulum of hepatocyte• Results in cirrhosis of liver

• Role as tumour marker• As an inhibitor of fibrinolysis

α2 globulins

CeruloplasminIt is a copper containing α2

globulinIt is a glycoprotein having 8 sites

for copper bindingNormal level in plasma is 25-

50mg/dlIt has enzyme activities

Functions of ceruloplasmin

• Contains 90% of total serum copper

• Acts as ferroxidase and helps in oxidation of Fe2+ to Fe3+ which can be incorporated into transferrin

Clinical significance

• Increase• In pregnancy, inflammatory

diseases, malignancy, oral oestrogen therapy and contraceptive pills

• Dercrease• In wilson disease and in menke’s

disease

Haptoglobin

• Formed by two types of polypeptide chains

• Two α chains ( possibly 3) and only one form of β chain.

• Synthesised in liver by hepatocytes

Function

• Binds with free Hb and minimises urinary loss of Hb

• Combining power of Hp with free Hb varies with different phenotypes

• After binding Hp-Hb complex circulates in blood which cannot pass through glomerular filtrate.

Clinical significance

• Concentration is increased in inflammatory diseases

• Mismatched blood transfusion• To evaluate the rheumatic

diseases

β-globulin

• β lipoprotein• Transferrin• True carrier of Fe• Site of synthesis is the liver• Functions• Transport Fe from the intestine

to site of synthesis of Hb• Unsaturated transferrin has a

bacteriostatic function

C reactive protein

• It precipitates with group C polysaccharide of pneumococci in the presence of Calcium ions

• Clinical significance• Binds to heme and bears some

chemical and antigenic relation to liver catalysis

• Bind to T lymphocyte and activate complement

• A role in the formation of heme • Non-specific indicator of inflammation• It remains increased in solid tumours

hemopexin• Synthesised by the parenchymal cell

of liver• Functions• Binds and removes circulating heme

from breakdown of Hb• Clinical significance• Inceases during pregnancy, diabetes

mellitus,• Duchenne muscular dystrophy and

melanomas• Decreases in hemolytic disorders, at

birth in new borns,

β2 microglobulins

• Increased in renal diseases and it is a reflection of impairment of function of glomerular membrane or renal tubules

• Tumour marker

• Urinary β2 M in Wilson disease, chronic nephritis, poisoning

• β2 M in serum in chronic nephritis, malignant tumors, abnormal pregnancy, chronic rheumatism

IgD

IgM IgA

IgG

IgE

γ globulins

reference

• Internet• Shinday• harper

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