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Lecture 1:

Plasmatic proteins

2009-2010
Content of lecture 1:

1. Structure, function and production of plasmatic proteins.


2. Quantitative changes of plasmatic proteins (hypo and
hyperproteinemias)
3. Electrophoretic separation of plasmatic proteins. Disproteinemias.
4. Disproteinemia in acute phase reaction
5. Disproteinemia in chronic inflammation
6. Disproteinemia in nephrotic syndrome
7. Disproteinemia in exudative enteropathy
8. Disproteinemia in monoclonal gammopahties
9. Disproteinemia in hypo gamma globulinaemia
10. Deficiency of specific proteins: alfa1 antitrypsine, antithrombin III
1.1. Structure, function and production of
plasmatic proteins
Proteins are made of aminoacids, bound
together by peptide bonds:

• primary structure (= secvenţa reziduurilor


de aminoacizi din lanţul polipeptidic),

• secondary structure (alpha-helix, beta –


sheet, a local conformation stabilized by
hydrogen bonds),

• Tertiary structure (the overall shape of a


single protein molecule)

• Quaternary structure (the structure


formed by several protein molecules
(polypeptide chains), usually called protein
subunits).
1.2. Cellular localization and Synthesis of proteins
1.3. Protein in nutrition

 Most microorganisms
and plants can
biosynthesize all 20
standard amino acids,
 Animals (including
humans) must obtain
some of the amino
acids from the diet.
 The amino acids that
an organism cannot
synthesize on its own
are referred to as
essential amino acids
.
1.4. Meabolism of proteins

 Catabolism of proteins by:


 Denaturation (acid)
 Hydrolysis (proteases)

Some ingested amino acids are used for protein biosynthesis, while others are
converted to glucose through gluconeogenesis, or fed into the citric acid cycle.
This use of protein as a fuel is particularly important under starvation
conditions as it allows the body's own proteins to be used to support life,
particularly those found in muscle
2. Quantitative changes of plasmatic
proteins (hypo and hyperproteinemias)

 Hypoproteinemia is mainly associated with hypoalbuminemia


 Hyperproteinemia is mainly associated with hyperglobulinemia

 In the past were used tests to identify which fraction is increased


(Tymol test, Kunkel test, ZnSO4 test) – these tests were orientative,
not precise.

 Electrophoretic separation of proteins is used to identify a syndrome,


not to indicate the cause.
PROTEINE TOTALE SERICE. PROTEINOGRAMA
PRINCIPALELE PROTEINE PLASMATICE
 Peste 90 de proteine au fost izolate şi purificate din sânge.
 Separarea proteinelor ( în funcţie de sarcină, mărime), pe un suport solid, într-un câmp electric = proteinogramă.

FRACŢIUNEA % G/100ML
1 Albumina 52 – 60 3,5 – 5,5
2 α1 globuline 3–5 0,25 – 0,35
3 α 2 globuline 8 – 10 0,5 – 0,75
4 β globuline 12 – 14 0,8 – 1,05
5 γ globuline 16 - 20 1,1 – 1,5
Electrophoretic separation of plasmatic proteins.
Disproteinemias
 A change in Albumin/ Globulin ratio.
 Ratio can be modified even at a normal protein
concentration!
 Classification of disproteinemia:
 With normal TP (total protein) concentration
 Acute phase reaction, Chronic inflammation

 With decreased TP concentration


 Nephrotic syndrome, liver cyrrhosis, exudative

enteropathy
 With increased TP concentration
 Multiple myeloma, Waldenström disease, Light chains

disease
Disproteinemia in acute phase reaction
Change in Acute-Phase Reactants After a Moderate Inflammatory Stimulus
Change in Plasma Concentration (%)

30,100
Serum amyloid A
30,000 C-reactive protein
700
600 Haptoglobin

500 Fibrinogen

400 C3
Albumin
300
Transferrin
200
100
0

0 7 14 21
Time After Inflammatory Stimulus (days)
Gabay C, Kushner I. N Engl J Med. 1999;340:448-454.
Disproteinemia in chronic inflammation
Disproteinemia in nephrotic syndrome, liver
cyrrhosis, exudative enteropathy
Disproteinemia in monoclonal gammopahties
Disproteinemia in hypo gamma globulinaemia

 Hypogammaglobulinemia is a disorder that is caused


by a lack of B-lymphocytes and a resulting low level
of immunglobulins (antibodies) in the blood
 The most common congenital abnormalities of B
lymphocyte production include:
 Hypogammaglobulinemia (Common Variable
Immunodeficiency)
 Ig A Deficiency
 X-linked Agammaglobulinemia (Bruton Disease)
 Transient hypogammaglobulinemia of infancy
Disproteinemia in hypo gamma globulinaemia

 Chronic infections: Giardia lamblia, bronchitis and sinusitis. These


infections respond to antibiotics but reoccur upon discontinuation of
the medications.

 Chronic diarrhoea (including protozoan and parasitic infections).

 Atrophic gastritis with pernicious anemia.

 Villous atrophy in the small intestine, which can resemble coeliac


disease and cause diarrhoea and malabsorption;
inflammatory bowel disease.

 Polyarthritis, or joint pain, spread across most joints, but specifically


fingers, wrists, elbows, toes, ankles and knees.

 Fatigue, Malabsorption, Weight loss.


How is it diagnosed?

Some tests that indicate hypogammaglobulinemia


include:
 Low serum immunoglobulins and B lymphocytes
 Missing specific antibodies to any vaccines the
child has received
 Absence of antibodies to A and B blood group
antigens
Deficiency of specific proteins: alfa1 antitrypsin

 is a genetic disorder caused by defective production of


alpha 1-antitrypsin (α1AT), leading to decreased α1AT activity in
the blood and lungs, and deposition of excessive abnormal
A1AT protein in liver cells.

 There are several forms and degrees of deficiency. Severe


α1AT deficiency causes panacinar emphysema in adult life in
many people with the condition (especially if they are exposed
to cigarette smoke), as well as various liver diseases in a
minority of children and adults.

 It is treated by avoidance of damaging inhalants, by


intravenous infusions of the α1AT protein, by transplantation of
the liver or lungs.
Deficiency of specific proteins: antithrombin III

 Antithrombin III deficiency is a rare


hereditary disorder that generally comes to light when a
patient suffers recurrent venous thrombosis and
pulmonary embolism. Inheritance is usually autosomal
dominant, though a few recessive cases have been
noted.

 In renal failure, especially nephrotic syndrome,


antithrombin is lost in the urine, leading to a higher
activity of Factor II and Factor X and in increased
tendency to thrombosis.
DETERMINATION METHODS FOR PROTEINS

 IMMUNOFLUORESCENCE – (AB (AB antinuclear), Ag


tisular
 LATEX AGAGGLUTINATION
GLUTINATION – CRP, FR, Ac antiDNA
antiDNA
 ELISA, RIA – hormons
hormons
 IMM
IMMUNODIFUSION
UNODIFUSION – for identification
identification of Ag or
Ab
 ELECTROPHORESIS
ELECTROPHORESIS - proteinogram
 COLORIMETRY
COLORIMETRY – total protein, albumin
 NEPH
NEPHELOMETR
ELOMETRYY – Fibrinogen, Imunglobulins
Imunglobulins