Plasma protein haptoglobin

Be familiar with, know the function of, and know the diagnostic significance of the following plasma proteins haptoglobin, hemopexin, albumin, fibrinogen, immunoglobulins, a-1-antitrypsin, and complement. 

Table 50-2 summarizes the functions of many of the plasma proteins. The remainder of the material in this chapter presents basic information regarding selected plasma proteins albumin, haptoglobin, transferrin, ceruloplasmin, aj-antitrypsin, aj i roglobulin, the immunoglobulins, and the complement system. The lipoproteins are discussed in Chapter 25. 

The vague definition offered above or rather these characteristics appear to be sufficient since no plasma protein capable of forming a strong bond with Hb is known to occur in mammalian plasma except those mucoproteins with the general biochemical properties originally accepted as characteristic of haptoglobins. 

In the later discussion of the method for measuring Hp it is considered as established that haptoglobins are the only native plasma proteins which exist or may exist in normal or pathological mammalian plasma with a HbBC above 5 mg/100 ml, i.e., the lowest capacity measurable by routine methods. It is also assumed that native haptoglobins themselves have no affinity for heme. The suggestion by Jones et al. (J14) that rabbit Hp has affinity for heme still lacks supportive evidence and can therefore not yet be accepted. 

In healthy individuals, the concentration of plasma proteins is constant. Diseases in organs that are involved in protein synthesis and breakdown can shift the protein pattern. For example, via cytokines (see p. 392), severe injuries trigger increased synthesis of acute-phase proteins, which include C-reac-tive protein, haptoglobin, fibrinogen, complement factor C-3, and others. The concentrations of individual proteins are altered in some diseases (known as dysproteinemias). 

The tetramer free dimer dissociation constant, off. is measured in the presence of haptoglobin (Hp), which is a plasma protein that binds two free dimers rapidly and essentially irreversibly (13). The reaction of Hp with Hb that contains deoxy subunits can be followed by UV/visible spectroscopy, whereas the Hp reaction with fully ligated Hb, which has no appreciable... 

The acute-phase response consists of increased production of a group of plasma proteins in response to tissue injury or inflammation. Important acute-phase reactants are the C-reactive protein, serum amyloid haptoglobin, hemopexin,... 

Hulsewe et al. 1997). Several of the plasma proteins that alter in hepatotoxicity include hhrinogen, haptoglobin, transferrin, ceruloplasmin, alphaj-macroglobulin, coagulation cascade and complement proteins, secretory IgA, carbohydrate deficient transferrin (CDT), and protein F (see Chapter 8). 

Modifications of the expression of plasma proteins can be related to genetic variations, complex combinations of post-translational modifications, alterations directly or indirectly related to diseases, or combinations of these mechanisms. Genetic variants of proteins such as haptoglobin, Gc-globulin, apolipoprotein E, apolipoprotein A-1, transferrin, or alpha-1-antitrypsin can be identified using 2-DE (Anderson and Anderson, 1979 Rosenblum et al, 1983 Tissot et al, 1993b Tissot et al, 2000b). 

A seventh vitamin K-dependent protein, protein Z, has been isolated from plasma (123). Protein Z is closely related to the factor IX-like proteases, factors VII, IX, X and protein C, consisting of the Gla domain, the two EGF units and a single Hya residue. However, similar to the heme binding protein haptoglobin, protein Z has no associated proteolytic activity as the two of the three essential catalytic residues have been modified (123). In contrast to protein sequencing, cDNA analysis allows the prediction of the amino acid sequence of the primary translation product of the mRNA species. Post-translational modifications are not detected, but precursor structures are elucidated. The vitamin K-dependent clotting factors are synthesized as precursors with leader sequences of 38 to 46 amino... 

Determination of acute-phase proteins (CRP, orosomucoid, haptoglobin, transferrin, prealbumin), immunoglobulins (IgA, IgG, IgM), compressive markers (albumin, fibrinogen), markers of tissue destruction (Apo A-I, A-II, Apo B), components of complement (C3, C4), proteinase inhibitors (antithrombin HI, a -antitrypsin). The measurement was performed simultaneously in CSF and in serum (plasma) by a laser nephelometric method. The functional state of the blood-CSF barrier was evaluated numerically with the help of the quotient Q = Albcsp/s and also by the intrathecal synthesis of immunoglobulins according to Reiber s formula and for each class—IgG, IgM, IgA. 

Multiple polyclonal lAC has been applied for the selective removal of high-abundance proteins such as human semm albnmin and immnnoglobnlins, from human plasma samples [10-11]. The approach has been extended to immunodepletion of transferrin, haptoglobin, and antitrypsin as well and commereiahzed [19]. The efiectiveness of some commercial kits in plasma and cerebrospinal finid was evalnated by Ramstrom et al. [20]. 

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