Ethan A. Natelson

Plasma Protein Survey

When blood is drawn, allowed to clot, and centrifuged, the supernatant obtained is called serum. Serum, in addition to other components, contains all the proteins of the blood other than those involved in the clotting mechanism (mainly fibrinogen) and the cell proteins. If the blood is mixed with an anticoagulant, such as heparin, or a calcium complexing agent, such as sodium fluoride or ethylene diamine tetraacetate, and then centrifuged, the supernatant obtained is called plasma and contains all the proteins of serum, plus fibrinogen and other clotting factors. The proteins of the plasma may be divided into three main categories: albumin, the clotting factors (including fibrinogen), and the globulins. The globulins include the proteins of the complement system, the immunoglobulins, and numerous other proteins with special functions (Table 3.1).

Prealbumin II: Vitamin A(Retinol)-Binding Protein

Vitamin A circulates in the blood in the form of the alcohol called retinol. Retinol is found bound to prealbumin on electrophoresis.(1) It was soon shown that the retinol-binding protein (RBP) of prealbumin which held the retinol was tightly bound to thyroxine-binding prealbumin (TBPA) in a 1:1 molar ratio. This complex of RBP and TBPA is the retinol transport system.(2–4) Figure 12.1 is a schematic representation of this complex.

Hemopexin: Iron Recycling

There is a significant amount of methemoglobin circulating in human plasma at all times. In this compound, the iron in the iron-porphyrin complex is in the trivalent state and does not participate in oxygen exchange. The prosthetic group is called ferriprotoporphyrin IX. The free base is called hematin, and the chloride salt hemin (see Volume 2, p. 469). Some use the expressions ferriheme for ferriprotoporphyrin IX and ferrihemoglobin to signify methemoglobin.

Steroid Hormone-Binding Proteins

Steroid hormones bind to albumin but with low affinity, that is, with a relatively high dissociation constant (about 10−4) . However, because of albumin’s high concentration in the serum, this binding is of substantial significance.(1) The binding capacity of plasma albumin for the steroid hormones is far in excess of the physiological steroid hormone concentration.

Prealbumin I: Iodothyronine-Binding Proteins

Prealbumin is predominantly a complex of thyroxine-binding prealbumin and retinol-binding protein. Thyroxine-binding prealbumin is well characterized and will be discussed first. For convenience, the nature of thyroxine binding globulin will also be discussed since the function of these two proteins is interrelated.

Ceruloplasmin: Copper Metabolism

Ceruloplasmin (ferroxidase I) first described in 1948, is the blue copper-containing oxidase present in the α2-globulin fraction of human serum (see Figure 3.5, Table 3.1). Close to 95% of the serum copper is located in this fraction.(1,2) The molecular weight of the major form of ceruloplasmin, referred to as ceruloplasmin I, is 134,000 ± 3000.(3) Consistent with its molecular weight, its sedimentation coefficient is 7.25s and diffusion coefficient 4.46 × 10 −7 cm2/sec. There are about 1065 amino acid residues in the molecule. The amino acid composition has been determined (Table 8.1).(3,4) Substantial progress has also been made in sequencing the molecule.(5,6)

Haptoglobins: Hemoglobin Binding

Certain proteins appear in the plasma in increased amounts during inflammatory reactions. These are often referred to as the acute phase reactants.(1) See Section 5.7. Generally, these proteins are glycoproteins synthesized in the parenchymal cells of the liver which contain substantial amounts of carbohydrate attached to the protein molecule. They are precipitable by adding about 150 times the volume of 95% ethanol to serum.(2) The C-reactive protein of serum is a typical example (see Section 5.7.1).

Transferrin: Iron Metabolism

By their very nature all plasma proteins will tend to bind anions and cations and various types of organic compounds. Almost every type of bond, including primary and secondary valences and Van der Waals forces are employed for this purpose. Thus there are polar bonds, such as in salt formation with anions or cations, since proteins are amphoteric in nature. With semipolar bonds chelate formation occurs, especially when binding metal ions. Hydrogen bonding is common since the oxygen on the carbonyl group and the nitrogen of the amide both will bind protons. Insertion of hydrocarbon portions of a molecule into a hydrophobic pocket formed in a protein fold is common. This is used in treating proteins with dodecyl sulfate so as to provide a uniform electrical charge for all proteins, in acrylamide gel electrophoresis.

Protein Composition and Properties

Before discussing the plasma proteins, it is advantageous to first review the fundamental chemistry of the proteins in general.

Lipoproteins in Nutrition and Transport

Before discussing the lipoproteins, it is necessary to identify the nature of the lipids being transported by these proteins.