PLASMA PROTEINS AND BLOOD CLOTTING
Albumin
-the most common protein in plasma -single chain protein of 67,000 molecular weight -contributes 80% of colloid osmotic pressure -serves for transport and as a reservoir for small molecules and ions. -metabolites like bilirubin travel in the blood w albumin.
Globulins: The alpha 1
-high density lipoprotein (HDL) -thyroxine binding globulin -retinol binding protein -antitrypsin -antichymotrypsin.
Blood clotting: Role of Proteolytic Cleavage
-All but 3 of the activated clotting factors are serine proteases. -have mechanisms like chymotrypsin. -They use a charge-like network at their active sites to increase the nucleophilicity of a key serine residue which can attack the peptide carbonyl group.
BLOOD CLOTTING DISORDERS
-Factor V Leiden mutation -von Willebrand factor -Hemophilia A -Hemophilia B
Fibrinogen and Fibrin
-One of the terminal events in blood clotting. -Fibrinogen normally constitutes 4-6% of total plasma protein.
factor 10
-activation of factor 10 is used for both intrinsic and extrinsic pathways -activated factor 10 with conjunction to 5 factor makes conversion of prothrombin to thrombin which makes fibrinogen to fibrin.
alpha 2 globulins
-haptoglobin -ceruloplasmin -prothrombin -macroglobulin.
beta globulins
-hemopexin -transferrin -low-density lipoproteins (LDL).
Anticoagulants
1. Compounds that bind calcium such as EDTA, oxalate, citrate and fluoride. (form insoluble salts w ca ions). 2. Heparin enhances the formation of inactive complexes of antithrombin III with thrombin and other clotting factors. (inhibiting the rxn from fribrinogen to fibrin). 3. Dicoumarol and warfarin are structurally (analogs) similar to vitamin K and inhibit carboxylation of glutamate to give g-carboxyglutamyl residues in prothrombin and other blood-clotting factors which bind calcium. (inhibition of blood clotting and dissilution of clot).
Normal plasma contains
60-80 g protein per liter. Of this about 45 g is albumin and 20-30 g is composed of a mixture of globulins.
Blood Clotting: Significance of clot formation and dissolution
A critical balance is necessary between hemostasis and hemofluidity.
Functions of Plasma Proteins
A. Transport molecules B. Colloid Osmotic Pressure C. Iron and Heme Metabolism D. Protease Inhibitors E. Coagulation F. Immune Response
Cross-link Formation
Factor 13a is a transglutaminase that catalyzes the formation of cross-linking amide bonds between lysine and glutamine residues: -The resulting cross links cause the conversion of a soft clot to a hard clot
plasma proteins: Iron and Heme Metabolism
Hemopexin and haptoglobin bind heme and hemoglobin, respectively, to form complexes which are not excreted by the kidney and which can be transported to the liver for further processing. (prevent loss of renal function)
gamma globulins
Immunoglobulins, group that are not associated w liver synthesis but w liver mal function you see a shift in these ratios.
plasma proteins: Transport molecules
In addition to albumin this group includes transferrin for the transport of iron and ceruloplasmin for the transport of copper. Lipoproteins serve in lipid transport.
The major groups of plasma proteins are
albumin and alpha 1, alpha 2, beta and gamma globulins. However, functional classification is not related to electrophoretic classification.
Several of the factors in blood clotting require
calcium for activity
a clot is strengthen by
covalent cross linking between fibrin molecules, catalized by activated factor 13.
kiniogen and kallikrein
damaged factors of the intrinsic pathway
The clotting proteases are inhibited by serine protease inhibitors such as
diisopropylfluorophosphate (DFP).
alpha 1 antitrypsin globulin
functionally critical role in elastin inhibition
Blood clotting: intrinsic factor (damage surface)
initial factor activation of factor 12 to its activated form. Then you go 11, 9, 10. T activate 10 you need activated factor 9 w factor 8.
Hemofluidity
involves clotting inhibition and clot dissolution which is important in the healing process.
Hemostasis
involves platelet aggregation, vasoconstriction and coagulation.
Blood clotting: extrinsic pathway (trauma)
is activated by factor 7. then 10 to activated factor 10. Shorter than intrinsic pathway.
Hemophilia A
is caused by a deficiency of Factor VIII, inherited in an X-linked recessive pattern.
von Willebrand factor
most common cause of decreased blood clotting activity. Mediates platelet adhesion to the extracellular matrix and it binds factor VIII in the plasma , preventing its degradation.
Factor V Leiden mutation
mutation that increase the body's blood clotting process. Causing a resistance to inactivation by Protein C, a protein that keeps the formation of blood clots in check.
Hemophilia B
results from a deficiency of Factor IX, inherited in an X-linked recessive pattern.
Clot dissolution is caused by
the action of plasmin which is a protease that acts on the fibrin network. Plasmin is derived from plasminogen by the proteolytic action of plasminogen activators activators.
thrombin
the conversion of fibrinogen (Factor I) to fibrin is catalyzed by
Plasma proteins are synthesized in
the liver or reticuloendothelial cells. globulins are associated with the reticuloendothelial cells.
The classification of plasma proteins is based on
their electrophoretic properties.
