PROTEINS OF BLOOD PLASMA

Among the most studied of all proteins are those present in blood plasma. Their ready availability and the clinical significance of their study led to the early development of electrophoretic separations. Electrophoresis at a pH of 8.6 (in barbital buffer) indicated six main components. The major and one of the fastest moving proteins is serum albumin. Trailing behind it are the 1-, 2-, and -globulins, fibrinogen, and -globulins. Each of these bands consists of several proteins and two-dimensional separation by electrophoresis and isoelectric focusing reveals over 30 different proteins.e Many of these contain varying numbers of attached carbohydrate units and appear as families of spots.
Fractionation of large quantities of plasma together with immunochemical assays has led to identification of over 200 different proteins. Sixty or more are enzymes, some in very small quantitites which may have leaked from body cells. Normally plasma contains 5.7 – 8.0 g of total protein per 100 ml (~1 mM). Albumin accounts for 3.5 – 4.5 g/100 ml. An individual’s liver synthesizes about 12 g each day. Next most abundant are the immunoglobulins. One of these (IgG or γ-globulin) is present to the extent of 1.2–1.8 g/100 ml. Also present in amounts greater than 200 mg per 100 ml are - and -lipoproteins, the 1 antitrypsin, 2-macroglobulin, haptoglobin, transferrin, and fibrinogen.
Plasma proteins have many functions. One of them, fullfilled principally by serum albumin, is to impart enough osmotic pressure to plasma to match that of the cytoplasm of cells. The heart-shaped human serum albumin consists of a single 65 kDa chain of 585 amino acid residues coiled into 28 helices. Three homologous repeat units or domains each contain six disulfide bridges, suggesting that gene duplication occurred twice during the evolution of serum albumins. The relatively low molecular mass and high density of negative charges on the surface make serum albumin well adapted for the role of maintaining osmotic pressure. However, serum albumin is not essential to life.



Over 50 mutant forms have been found and at least 30 persons have been found with no serum albumin in their blood. These analbuminemic individuals are healthy and have increased concentrations of other plasma proteins.
A second major function of plasma proteins is transport. Serum albumin binds to and carries many sparingly soluble metabolic products, including fatty acids, tryptophan, cysteine, steroids, thyroid hormones, Ca2+, Cu2+, Zn2+, other metal ions, bilirubin, and various drugs. There are also many more specialized transporter proteins. Transferrin carries iron and ceruloplasmin (an α2 globulin) transports copper. Transcortin carries corticosteroids and progesterone, while another protein carries sex hormones. Retinol-binding protein carries vitamin A and cobalamin-binding proteins vitamin B12. Hemopexin carries heme to the liver, where the iron can be recovered.j Haptoglobin binds hemoglobin released from broken red cells and also assists in the recycling of the iron in the heme.k Lipoproteins carry phospholipids, neutral lipids, and cholesterol esters. Most of the mass of these substances is lipid.
Immunoglobulins, α1-trypsin inhibitor and 2-macroglobulin, ten or more blood clotting factors; and proteins of the complement system all have protective functions that are discussed elsewhere in this book. Hormones, many of them proteins, are present in the blood as they are carried to their target tissues. Many serum proteins have unknown or poorly understood functions. Among these are the acute phase proteins, whose concentrations rise in response to inflammation or other injury.