Blood plasma
- 5 % of body weight:
- 55 % of blood volume
- 25 % of extracellular fluid volume
- composition:
- 93 % = water
- 6 % = organic compounds
- 1% = inorganic compounds
- Na+ = main extracellular cation, osmotic
pressure
- K+ = main intracellular ion, excitability
- Ca2+ = both ionized and bound to the proteins
of blood plasma
- Cl- = volume of blood plasma, pH, osmotic
pressure
- HCO3- = buffering system, transport of carbon
dioxide
Plasma proteins
- concentration 65 – 80 g  l (<300 proteins)
- 35 – 50 g/l = albumin
- 20 – 35 g/l = serum globulins
- biosynthesis:
- liver (most)
- lymphocytes (immunoglobulins)
- enterocytes (e.g. apoprotein B-48)
- degradation:
hepatocytes, mononuclear phagocytic system (complexes of antigen-antibody, hemoglobin-haptoglobin)
Types of plasma proteins
1. Albumin
2. Globulins
a-globulins : a1 and a2-globulins
b-globulins: b1 and b2-globulins
g-globulins
3. Fibrinogen
b1 b2
+ -
albumin
a1 a2
g-globulins
Elfo fractions of plasma proteins
Fraction Rel. amount
(%)
c (g/l)
Albumins: albumin
pre-albumin (transthyretin)
52 – 58 34 – 50
a1-globulins: thyroxin-binding globulin, transcortin,
a1-acid glycoprotein, a1-antitrypsin, a1-lipoprotein (HDL),
a1-fetoprotein
2,4 – 4,4 2-4
a2-globulins: haptoglobin, macroglobulin, ceruloplasmin 6,1 – 10,1 5 – 9
b-globulins: transferrin, hemopexin, lipoprotein (LDL),
fibrinogen, C-reactive protein, C3 and C4 components of
the complement system
8,5 – 14,5 6 – 11
g-globulins: IgG, IgM, IgA, IgD, IgE 10 – 21 8 – 15
Functions of plasma proteins
• Transport:
• albumin – fatty acids, bilirubin, calcium, drugs
• transferin – iron
• ceruloplasmin – copper
• transcortin – cortisol, corticosterone
• lipoproteins – lipids
• haptoglobin – free hemoglobin
• thyroxin binding globulin – thyroxin
• retinol binding protein – retinol
• Osmotic regulation:
• Plasma proteins are colloidal and non-diffusable and exert a colloidal osmotic pressure, which helps to
maintain a normal blood volume and a normal water content in the interstitial fluid and the tissues.
• Albumin content is most important in regulation of colloidal osmotic or oncotic pressure.
• Decrease in albumin level results in loss of water from blood and its entry into interstitial fluids causing edema.
• Catalytic function (= enzymes):
• e.g lipases for removal of lipids from the blood
Functions of plasma proteins (cont.)
• Blood clotting:
• Many factors are involved in clotting mechanism and prevent loss of excessive
amount of blood; e.g. clotting factors IX, VIII, thrombin, fibrinogen etc.
• An excess of deficiency leads to a disease; e.g. hemophilia, thrombus
formation
• Anticoagulant activity (thrombolysis):
• Plasmin breaks down thrombin and dissolves the clot
• Buffering capacity:
• Proteins in plasma help to maintain acid-base balance
General properties of plasma proteins
• Most are synthesized in the liver
• Exception: g-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…)
Acute phase reactants (APRs)
• Their levels change during acute inflammatory
response
• Cause conditions where there is:
✓ the destruction of cells
✓ the reversible cell damage and subsequent repair
✓ the metabolic activation of certain cells (immune
cells)
• APRs concentration changes in:
• infection
• surgery
• injury
• cancer
Albumin
▪ Concentration in plasma: 45 gl
▪  60% of the total plasma protein
▪ Functions:
• maintenance of plasma oncotic pressure
(values ​​lower than 20 g leads to edema)
• protein reserve, the source of amino acids
• transport of:
• steroid hormones
• free fatty acids
• bilirubin
• drugs (sulfonamides, aspirin)
• Ca2+
• Cu2+
Albumin
• synthesized as a preproprotein
• Alb – chain of 585 AA, 17 disulfide bonds
• proteases – subdivide into 3 domains,
which have different functions
• ellipsoidal shape – does not increase the
viscosity of plasma X fibrinogen
http://what-when-how.com/molecular-biology/serum-albumin-molecular-biology/
preproalbumin proalbumin
signal
peptide hexapeptide albumin+ +
furin
signal
peptidase
Causes of Albumin Deficiency
• Liver diseases (cirrhosis) – decrease in the ratio of albumin to
globulins
• Protein malnutrition
• Excessive excretion by kidneys (renal disease)
• Mutation causing analbuminemia (affects splicing)
Merlot AM, Kalinowski DS, Richardson DR: Unraveling the mysteries of serum albumin-more
than just a serum protein. Frontiers in Physiology 2014, 5.
a1-antitrypsin
• Main globulin of a1 fraction (90 %)
• is synthesized in the liver in
hepatocytes and macrophages
• glycoprotein, highly polymorphous
(≈75 forms)
• Function:
• Main plasma inhibitor of serine proteases
(trypsin, elastase...)
• during the acute phase increases 
inhibition of degradation of connective
tissue by elastase
• deficiency  proteolytic lung damage
(emfyzem)
Transferrin
• Transferrin is a β-globulin
• It binds free iron in serum
• Normally it is about one third saturated
with iron
• Transferrin levels are decreased in:
• liver disease (e.g. cirrhosis)
• Chronic infections
• Nephrosis
• Congenital atransferrinaemia
• Increased serum transferrin levels occur
during increased transferrin synthesis
caused as a result of iron deficiency
anemia
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
transferrin (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 reenters
plasma.
Transferrin
• Free Fe2+ ions are toxic for organism – catalyses Fenton reaction (formation of
highly toxic OH radical)
H2O2 + Fe2+ → OH- + ˙OH + Fe3+
• Transferrin with other plasma proteins that bind iron or heme, acts as an
antioxidant (prevents ROS)
• Causes of decline in transferrin :
• burns, infections, malignant processes and liver and kidney diseases
• Cause of relative transferrin excess:
Iron-deficiency anemia
Ferritin
▪ Intracellular protein; only small portion in plasma
▪ 24 subunits surround 3000 - 4500 ions of Fe3+
▪ Function: stores iron that can be called upon for use
when needed
▪ Primary hemochromatosis – genetic disorder
characterized by increased absorption of iron from
the intestine  accumulated iron damages organs
such as the liver, skin, heart, and pancreas.
Concentration of ferritin is elevated.
Ceruloplasmin
▪ Conc. in plasma: 300 mgl
▪ 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 plasma copper  albumin
may be more important in
copper transport (donates
copper to tissues more readily)
Copper is incorporated into ceruloplasmin during synthesis and is essential for oxidase activity. Within the plasma,
ceruloplasmin catalyzes the oxidation of the signaling molecule NO concomitantly with cupric (Cu2+) to cuprous (Cu1+)
reduction. Nitrite (NO2-) ions can therefore be used as a sink for NO production through reduction by deoxyhemoglobin,
which allows for the mobilization of NO as a signaling molecule involved in hypoxic vasodilation and ischemia-reperfusion
cytoprotection. In addition, nitrite acts independently as a signaling molecule necessary for cytoprotection and posttranslational
modifications such as iron nitrosylation and N-and S-nitrosation.
Haptoglobin (Hp)
▪ a2- globulin, tetramer a2b2 chains
▪ Exists in 3 polymorphic forms
▪ Functions:
▪ binds free hemoglobin and
delivers it to the
reticuloendothelial cells
▪ complex Hb-Hp is too large to
pass through glomerulus 
prevention of loss of free Hb (and
Fe)
Free Hb passes through glomerulus,
enters tubules and tends to
precipitate therein  kidney
damage
• Hp belongs to APRs 
• inflammation, infection
• injury
• malignancies
Causes of Hp increase
Causes of Hp decrease
• Hemolytic anemia:
• half-life of Hp = 5 days X of complex Hp-Hb = 90 min
(the complex is being rapidly removed from plasma)
 Hp levels fall when Hb is constantly being
released from red blood cells (as in hemolytic
anemias)
Delanghe JR, Langlois MR: Hemopexin: a review of
biological aspects and the role in laboratory medicine.
Clinica Chimica Acta 2001, 312(1-2):13-23.
Plasma proteins as antioxidants
Transferrin
Ferritin
Ceruloplasmin
Haptoglobin
Hemopexin (binds heme and transfers it to the liver)
act as antioxidants:
remove Fe 2+ and thus prevent the Fenton reaction:
H2O2 + Fe2+ → HO• + OH− + Fe3+
C-reactive protein (CRP)
• Belongs to b2-globulin, the levels of
which rise in response to
inflammation
• Acute-phase reactant
• Its physiological role is to bind to
phosphocholine expressed on the
surface of dead or dying cells (and
some types of bacteria)
• plasma concentration levels of CRP
rapidly increase within 2 hours of
acute insult, reaching a peak at 48
hours (bacterial, viral, fungal
infection, rheumatic diseases,
malignity, tissue necrosis)
Fibrinogen
• Glycoprotein, belongs to b2globulins
(Mr 340 000)
• Concentration in plasma - 1.5 –
4.5 g/l
• component of the coagulation
cascade – fibrin precursor
• acute-phase reactant ⇒ ↑
acute inflammation
Immunoglobulins
• Antibodies produced by B cells in
response to antigen stimulation
of the organism
• React specifically with antigenic
determinants
• Structure:
• consist of a minimum of 4
polypeptide chains - 2 heavy
(H) a 2 light (L) linked by
disulfide bridges
• light chains contain constant (C)
and variable (V) region
COOH
NH2
Ag
COOH
NH2
IgG
Plasma enzymes
1. Plasma specific enzymes:
cholinesterase,
plasma superoxid dismutase,
lecithin-cholesterol acyltransferase,
Serin proteases – inactive zymogens of coagulation factors and factors of
fibrinolysis (faktor II - prothrombin, factor VII, IX, XIII) and complement system
components, non-specific immune system (components C1 – C9).
Plasma enzymes (cont.)
Enzyma name abbrevi
ation
Causes leading to increased
levels
Alanine aminotransferase ALT liver and biliary tract disease
pancreatic disease
decompensated heart defects
Aspartate
aminotransferase
AST liver diseases
myokardium damage
disease of skeletal muscle and myocardium
Alkaline phosphatase ALP liver and biliary tract disease
bone diseases
Creatin kinase CK disease of skeletal muscle and myocardium
Lactate dehydrogenase LD1-5 Myocardium disease (LD1, LD2) and muscle disease
hepatopathy
g-glutamyl transferase GMT liver and biliary tract disease and
pancreatic disease