Globulin

Globulin refers to a heterogeneous group of globular proteins insoluble in water that are found in blood, eggs, milk, and as a reserve protein in seeds. Globular proteins are named for their approximately globe-shaped or spherical appearance and are the most abundant proteins in nature. Globular is one of the four major groups of protein structures with the others being fibrous, membrane, and disordered.An essential character common between seed and animal globulins is that they dissolve in dilute saline solutions (0.5-1.0 M NaCl). In animal fluids, globulins have diverse functions such as enzymes, antibodies, hormone regulation, nutrient transport, and contractile proteins. In plants globulins, the functions are mainly seed storage proteins and in plant cell dehydration/hydration.

Globulins found within the blood are produced by the liver and the immune system. Globulins have a higher molecular weight than albumins, which are another category of globular blood protein that makes up more than half of the total blood proteins. The primary blood proteins include globulin, albumin, and fibrinogen. Globulins have multiple purposes; the group includes immunoglobulins (antibodies), enzymes, carrier proteins, and complement. The total protein content of blood serum, obtained after removal of fibrinogen and most clotting factors, is 6 to 8 g/dl. Albumin, the most abundant component of serum, makes up 3.5 to 5.0 g/dl; globulin, the second most abundant component, makes up nearly the remainder of the protein content in serum. Albumen and globulin are involved in maintenance of osmotic pressure in the blood.

Globulins are divided into four groups based on how they migrate by electrophoresis. The four fractions of globulins include α1, α2, β and γ. Globulins are sometimes divided into only three fractions with only one alpha, beta, and gamma, and beta globulins are sometimes divided into β-1 and β-2 Alpha and beta globulins are produced in the liver and transport iron, lipids, and fat-soluble vitamins A, D, E, and K to cells. The gamma fraction contains the largest amount of immunoglobulin, also called antibody.

Most alpha and beta globulins are produce in the liver. Increases or decreases in the levels of certain globulin proteins are associated with disease.

High-density lipoprotein (HDL), also known as "good" cholesterol, is an alpha-globulin that absorbs cholesterol from the body and transports it to the liver for removal.

Sex hormone–binding globulin (SHBG), previously referred to as androgen-binding protein (ABP), is a beta globulin that transports and regulates androgens and estrogens. SHBG is found in the blood of all classes of vertebrates except for birds. In mammals, SHBG is mainly produced in the liver but genes that encode SHBG are also expressed at lower levels in the brain, kidney, uterus, and prostate.

Immunoglobulin, also known as immune globulin or gamma globulin, is the fraction of globulin in blood that contains antibodies produced by plasma B cells (also known as leukocytes) and plays a role in protection against bacteria, viruses, and fungi. The five types of human immunoglobulins are IgM, IgG, IgA, IgE and IgD.

The first isotype of antibody to be discovered was called gamma globulin because it was in the gamma region of mobility. It was later discovered that antibodies are also found in the alpha and beta mobility fractions. The Greek letter gamma was exchanged for the Roman G in the designation of the IgG class of immunoglobulins. IgG comprises 70-80% of blood immunoglobulins. IgG antibodies are produced in response to infection or antigen exposure. A few weeks post exposure, IgG levels rise, followed by a decreasing and stabilizing of levels. Upon re-exposure to the same antigen, IgG antibodies are rapidly reproduced and form the basis for long-term protection against microorganisms. IgG is the only immunoglobulin that passes to the placenta.

IgM was the second immunoglobulin isolated and this protein was originally called macroglobulin, discovered to be elevated in patients with the form of multiple myeloma called macroglobulinemia. IgM antibodies are produced in the body in response to a new infection or new “non-self” antigen and they increase for several weeks, providing short-term protection.

The IgA isotype was originally called beta2A-globulin and then shortened to alpha-immunoglobulin. Unlike IgG, the A does not stand for mobility in the alpha fraction of electrophoresis. IgA makes up 15% of the total blood immunoglobulins. IgA is also found in saliva, tears, respiratory and gastric secretions, and breast milk.

IgD was first discovered as an immunoglobulin elevated in a patient with multiple myeloma and did not react with antisera to known isotypes IgG, IgM and IgA.

IgE was named for the antibody reacting to antigen E, a fraction of pollen proteins known to elicit a potent erythema-wheal response on the skin. IgE is defined by the presence of the epsilon heavy chain. IgE is present at about 300-fold lower concentration compared with IgG. IgE is thought to be involved in defense against parasites, such as helminthes. IgE functions in a manner distinct from other immunoglobulins and activates mast cells and basophils through the cell-surface receptor Fc epsilon RI. Elevated IgE is associated with allergic disease, primary immunodeficiencies, infections, inflammatory diseases, and malignancies.

Immunoglobulins can be used as a form of immunotherapy purified form donated blood to treat immunological problems, antibody deficiencies, severe combine immunodeficiency disorders (SCID), multiple sclerosis, myasthenia gravis, Kawasaki disease, systemic lupus erythematosus (SLE), and organ transplantations. To treat infections, antibodies from the blood of a person recovered from an infection can be given as a therapy in the form of convalescent plasma, convalescent serum, or hyperimmune immunoglobulin, which is a concentrated antibody product.

Globulins stored in dicot and conifer seeds are separated into two main types—legumins and vicilins, with sedimentation (S) coefficients of 11-12S and 7S, respectively. A sedimentation coefficient is a measure of the tendency of particles to settle out of solution, obtained in the analysis and separation of proteins by ultracentrifugation.In dicot seeds, 2S proteins include both globulins and albumins. The majority of total protein in many seeds consumed by humans are 7S and 11S globulins. Vicilin (7S) and legumin (11S) seed storage globulins belong to the cupin superfamily, one of four protein families that together contain nearly 60% of all plant food allergens. The discovery of the cupin superfamily is based on amino acid sequence similarities between wheat germin, fungal spheruins in slime mold (Physarum polycephalum) spores, and plant globulin seed storage proteins. Their shared structural feature is described as 6-stranded and the name cupin is derived from the Latin word “cupa” for barrel. The cupin core functions to provide stability in these proteins under extreme conditions.

A role for Wrightia tinctoria 11S globulin (WTG) was discovered in sequestering plant hormones that are needed for seed germination.

The unusual thermostability of cupins is linked to their resistance to digestion in the human gastrointestinal tract. The vicilin Ara h 1 and legumin Ara h 3 are major allergens that elicit immune responses in most individuals with peanut allergies. It has been reported that 90% of individuals allergic to peanuts have serum IgE that recognize Ara h 1. Approximately 34% of patients with peanut allergies are also allergic to tree nuts. This is thought to be related to shared IgE-binding epitopes between vicilin allergens in peanut and tree nuts and conserved regions in Ara h 1 between vicilin allergens.

Alpha-globulins found in cereal grains, in the prolamin superfamily of vascular plants, are nonallergenic.