Globulin

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The globulins are a family of globular proteins that have higher molecular weights than albumins and are insoluble in pure water but dissolve in dilute salt solutions. Some globulins are produced in the liver, while others are made by the immune system. Globulins, albumins, and fibrinogen are the major blood proteins. The normal concentration of globulins in human blood is about 2.6-3.5 g/dL.

Contents

The term "globulin" is sometimes used synonymously with "globular protein". However, albumins are also globular proteins, but are not globulins. All other serum globular proteins are globulins.

Types of Globulin

Schematic representation of a protein electrophoresis gel Electrophoresis.png
Schematic representation of a protein electrophoresis gel

All globulins fall into one of the following three categories :

Globulins can be distinguished from one another using serum protein electrophoresis.

Globulins exert oncotic pressure. Their deficiency results in loss of carrier functions of globulins, oedema due to decreased oncotic pressure, and susceptibility to infections due to decreased gamma-globulins (immuno-globulins) leading to decreased production of antibodies.

Globulins are mainly divided into three different sections depending on their electrophoretic mobility. The main sections for globulin would be the alpha globulins, beta globulin, and gamma globulin. The alpha globulins and the beta globulin are mainly created in the liver and the gamma globulin are made by lymphocytes and plasma cells in lymphoid tissue.

These globulins should consist of non-albumin proteins and there could be about a hundred different proteins that are included in the globulins. One group of proteins that are in the globulins is created in return for the inflammatory stimuli.

There is a certain equation to figure out the value of globulin. The equation goes by this Globulins = Total protein - Albumin since it should not have an albumin protein within the globulin. Usually, the concentration of globulin is measured either in grams per liter or milligrams per deciliter.

To check an accurate amount of immunoglobulins would be the radial immunodiffusion which replaced the immunoelectrophoretic which used to determine the accurate amount of immunoglobulin. [1]  

Globulins can be some of the most abundant storage proteins. Globulins have different solubilities such as the salt-soluble 7S and 11S-globulins. The solubility of globulins is determined by different fluorescence spectroscopy and urea sensitivity depending on the molecules that were studied. [2]

There was a study conducted to see the reaction of a human globulin with an erythrocyte surface which showed that a human globulin fixes to the erythrocytes in a non-related immune response fashion. Also, the globulin that was fixed on the erythrocyte has the trait to exchange with a globulin in a certain medium. [3]

Globulins aren't only a major blood protein, but can also be sex hormone-binding globulin. This type of globulin can transport androgens and estradiol in the blood. There is a specific receptor called SHBG-R that is on the membranes of the sex steroid-responsive cells which shows how it affects androgens and estradiol. [4]

Usually, proteins are dissolved in plasma and globulin is one of them. The protein serum consists of the serum protein which is about 6 to 8 g/dl then albumin makes 3.5 to 5.0 g/dl then the rest should be the globulins. The section where globulins fractions are located is made up of proteins, enzymes, and immunoglobulins. Usually, these compounds are arranged in the liver. The only difference would be the immunoglobulins which are arranged in the plasma cells.

These globulins are divided into four sections A1, A2, B, and Y. Certain migratory patterns are created by the levels of anode and cathode. If there is an increase in the globulin fraction it means there is also an increase in the immunoglobulins, but there can also be an increase in other proteins.

If there is a decrease in globulins it can be caused by malnutrition or congenital immune deficiency which can cause a decrease in protein in the kidney.

To see any decrease or increase in the levels of globulin fraction it should be done in the serum electrophoresis and be checked for any certain abnormalities. [5]

Globulins are usually tested through a blood test to see how much protein is in a patient's blood. The blood proteins that should be seen would be globulins and albumin. If a patient's protein level is very low there could be a possibility that the patient may have a liver or kidney disease since globulins are produced in the liver. There are two different types of blood tests. There is the total protein test or the serum protein electrophoresis which measures the level of each protein in a patient's blood. The serum protein electrophoresis test focuses more on the immune system and if it is working properly and it measures the levels of several types of globulins or proteins in the blood. [6]

This shows the levels of albumin and the different immunoglobulins Globulin Fractions.jpg
This shows the levels of albumin and the different immunoglobulins

The serum protein electrophoresis test measures the number of proteins in the serum part of a blood sample. The normal ranges to check for the serum globulin would be about 2.0 to 3.5 grams per deciliter then for the immunoglobulins A, M, and G have different ranges. If there are abnormal results then there are different possibilities on what it could mean either there is an acute infection, long-term inflammatory diseases, or Waldenström macroglobulinemia. [7]

Cremeren Globulins exist in various sizes. The lightest globulins are the alpha globulins, which typically have molecular weights of around 93 kDa, while the heaviest class of globulins are the gamma globulins, which typically weigh about 1193 kDa. Being the heaviest, the gamma globulins are among the slowest to segregate in gel electrophoresis.

The immunologically active gamma globulins are also called "immunoglobulins" or "antibodies".

As stated, globulins have different sizes, but the sex hormone-binding globulin has a molecular weight of 90 kDa. In certain subjects the sizes of the sex hormone differed from each other; some globulins had the size of 49 kDa, 52 kDa, and 56 kDa. The subjects with the higher molecular weight that was present showed that the subjects may have a genetic variant of this protein and that it is a heterozygote. This certain variant was discovered in both genders in children along with adults too. [8]

Human blood plasma levels

The normal concentration of globulins in human blood is about 2.3-3.6 g/dL.

Reference ranges for blood tests, comparing blood content of globulins (shown in purple at right) with other constituents. Blood values sorted by mass and molar concentration.png
Reference ranges for blood tests, comparing blood content of globulins (shown in purple at right) with other constituents.

Nonhuman globulins

Crystal structure of a pumpkin seed globulin Crystal structure of pumpkin seed globulin.png
Crystal structure of a pumpkin seed globulin

Globulin proteins exist not only in other animal species, but also in plants. Vicilin and legumin, from peas and other legumes, function as protein storage within seeds. These proteins can cause allergic reactions if they bind with human IgE antibodies. [9]

There have been multiple studies regarding globulins in different species because globulin is a protein that can be found in either plants or animals. These globulins could be found in cereal to legumes, something people can consume every day. Globulin would be a salt-soluble storage protein for plants. These globulins would be in two sections which should be 7S and 11S. [10]

The 7s globulin is in most plant species in a recent study it was discovered that the 7S is not a major seed storage protein as many researchers thought it was, but if not it was found to be a multifunctional protein that has a stress response, a hormone-like receptor and an antibacterial activity.

In the same study, it showed that Bg7S is the protein globulin that is soluble in certain high ionic strength of a salt solution that should have a high isoelectric point as well which should be around 9.05 to 9.26 pI.

This type of globulin is found in many different plants such as tomatoes, corn, wheat, and carrots. There was a genome sequence analysis performed on several plants to see if the gene Bg7S was present in each one and it showed that this gene was present in each plant that was tested meaning that this gene is universal in each plant. [11]

Pseudoglobulins and euglobulins

Pseudoglobulins are a class of globulins that are more soluble in ammonium sulfate than euglobulins. Pseudoglobulins are also soluble in pure water, while euglobulins are not. [12]

Related Research Articles

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

<span class="mw-page-title-main">Clinical chemistry</span> Area of clinical pathology that is generally concerned with analysis of bodily fluids

Clinical chemistry is a division in medical laboratory sciences focusing on qualitative tests of important compounds, referred to as analytes or markers, in bodily fluids and tissues using analytical techniques and specialized instruments. This interdisciplinary field includes knowledge from medicine, biology, chemistry, biomedical engineering, informatics, and an applied form of biochemistry.

<span class="mw-page-title-main">Globular protein</span> Spherical, water-soluble type of protein

In biochemistry, globular proteins or spheroproteins are spherical ("globe-like") proteins and are one of the common protein types. Globular proteins are somewhat water-soluble, unlike the fibrous or membrane proteins. There are multiple fold classes of globular proteins, since there are many different architectures that can fold into a roughly spherical shape.

<span class="mw-page-title-main">Blood plasma</span> Liquid component of blood

Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but which contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intravascular part of extracellular fluid. It is mostly water, and contains important dissolved proteins, glucose, clotting factors, electrolytes, hormones, carbon dioxide, and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood-related disorders.

<span class="mw-page-title-main">Gamma globulin</span> Class of blood proteins

Gamma globulins are a class of globulins, identified by their position after serum protein electrophoresis. The most significant gamma globulins are immunoglobulins (antibodies), although some immunoglobulins are not gamma globulins, and some gamma globulins are not immunoglobulins.

<span class="mw-page-title-main">Serum protein electrophoresis</span> Laboratory test

Serum protein electrophoresis is a laboratory test that examines specific proteins in the blood called globulins. The most common indications for a serum protein electrophoresis test are to diagnose or monitor multiple myeloma, a monoclonal gammopathy of uncertain significance (MGUS), or further investigate a discrepancy between a low albumin and a relatively high total protein. Unexplained bone pain, anemia, proteinuria, chronic kidney disease, and hypercalcemia are also signs of multiple myeloma, and indications for SPE. Blood must first be collected, usually into an airtight vial or syringe. Electrophoresis is a laboratory technique in which the blood serum is applied to either an acetate membrane soaked in a liquid buffer, or to a buffered agarose gel matrix, or into liquid in a capillary tube, and exposed to an electric current to separate the serum protein components into five major fractions by size and electrical charge: serum albumin, alpha-1 globulins, alpha-2 globulins, beta 1 and 2 globulins, and gamma globulins.

Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.

<span class="mw-page-title-main">Serum (blood)</span> Fluid and solute component of blood

Serum is the fluid and solute component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum includes all proteins not used in blood clotting; all electrolytes, antibodies, antigens, hormones; and any exogenous substances. Serum does not contain white blood cells (leukocytes), red blood cells (erythrocytes), platelets, or clotting factors.

<span class="mw-page-title-main">Transcortin</span> Protein found in humans

Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6, is a protein produced in the liver in animals. In humans it is encoded by the SERPINA6 gene. It is an alpha-globulin.

Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood proteins act as enzymes, complement components, protease inhibitors or kinin precursors. Contrary to popular belief, haemoglobin is not a blood protein, as it is carried within red blood cells, rather than in the blood serum.

<span class="mw-page-title-main">Serum albumin</span> Type of globular protein produced by the liver

Serum albumin, often referred to simply as blood albumin, is an albumin found in vertebrate blood. Human serum albumin is encoded by the ALB gene. Other mammalian forms, such as bovine serum albumin, are chemically similar.

The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells they can cause anemia; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a blood transfusion.

<span class="mw-page-title-main">Sex hormone-binding globulin</span> Human glycoprotein that binds to androgens and estrogens

Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it is called androgen-binding protein (ABP).

<span class="mw-page-title-main">Monoclonal gammopathy</span> Excess myeloma protein or monoclonal gamma globulin in the blood

Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, especially multiple myeloma. It is sometimes considered equivalent to plasma cell dyscrasia. The most common form of the disease is monoclonal gammopathy of undetermined significance.

<span class="mw-page-title-main">Albumin</span> Family of globular proteins

Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins are commonly found in blood plasma and differ from other blood proteins in that they are not glycosylated. Substances containing albumins are called albuminoids.

The Cohn process, developed by Edwin J. Cohn, is a series of purification steps with the purpose of extracting albumin from blood plasma. The process is based on the differential solubility of albumin and other plasma proteins based on pH, ethanol concentration, temperature, ionic strength, and protein concentration. Albumin has the highest solubility and lowest isoelectric point of all the major plasma proteins. This makes it the final product to be precipitated, or separated from its solution in a solid form. Albumin was an excellent substitute for human plasma in World War Two. When administered to wounded soldiers or other patients with blood loss, it helped expand the volume of blood and led to speedier recovery. Cohn's method was gentle enough that isolated albumin protein retained its biological activity.

<span class="mw-page-title-main">Fetal protein</span>

Fetal proteins are high levels of proteins present during the fetal stage of development. Often related proteins assume similar roles after birth or in the embryo, in which case the fetal varieties are called fetal isoforms. Sometimes, the genes coding fetal isoforms occur adjacent to their adult homologues in the genome, and in those cases a locus control region often coordinates the transition from fetal to adult forms. In other cases fetal isoforms can be produced by alternate splicing using fetal exons to produce proteins that differ in only a portion of their amino acid sequence. In some situations the continuing expression of fetal forms can reveal the presence of a disease condition or serve as a treatment for diseases such as sickle cell anemia. Some well known examples include:

Edestin, is a highly-digestible, hexameric legumin protein with six subunits, and a seed storage protein, with a molecular weight of 310 kDa. This protein is primarily found in hemp seeds. Edestin is a globular protein as opposed to fibrous protein (structural).

Blood plasma fractionation are the general processes separating the various components of blood plasma, which in turn is a component of blood obtained through blood fractionation. Plasma-derived immunoglobulins are giving a new narrative to healthcare across a wide range of autoimmune inflammatory diseases. This widespread applicability is anticipated to leverage market prospects for plasma fractionation, pegged to witness a noteworthy 7% CAGR. COVID-19 pandemic is expected to generate growth opportunities for the plasma fractionation market.

The liver plays the major role in producing proteins that are secreted into the blood, including major plasma proteins, factors in hemostasis and fibrinolysis, carrier proteins, hormones, prohormones and apolipoprotein:

References

  1. ↑ "Globulins". eClinpath. Retrieved 2023-04-26.
  2. ↑ "Web of Science". www.webofscience.com. Retrieved 2023-04-26.
  3. ↑ "Web of Science". www.webofscience.com. Retrieved 2023-04-26.
  4. ↑ Fortunati, N. (1999-03-01). "Sex Hormone-Binding Globulin: Not only a transport protein. What news is around the corner?". Journal of Endocrinological Investigation. 22 (3): 223–234. doi:10.1007/BF03343547. ISSN   1720-8386. PMID   10219893. S2CID   39594500.
  5. ↑ Busher, Janice T. (1990), Walker, H. Kenneth; Hall, W. Dallas; Hurst, J. Willis (eds.), "Serum Albumin and Globulin", Clinical Methods: The History, Physical, and Laboratory Examinations (3rd ed.), Boston: Butterworths, ISBN   978-0-409-90077-4, PMID   21250048 , retrieved 2023-04-26
  6. ↑ "Globulin Test: MedlinePlus Medical Test". medlineplus.gov. Retrieved 2023-04-26.
  7. ↑ "Blood and Plasma Proteins - Medical Biochemistry". doctorlib.info. Retrieved 2023-04-26.
  8. ↑ Gershagen, S (1987). ""Subunits of Human Sex Hormone Binding Globulin. Interindividual Variation in Size"". The Journal of Biological Chemistry. 262 (17): 8430–8437. doi: 10.1016/S0021-9258(18)47582-5 . PMID   3597380.
  9. ↑ SanchMonge, R.; Lopez-Torrejón, G.; Pascual, C. Y.; Varela, J.; Martin-Esteban, M.; Salcedo, G. (12 November 2004). "Vicilin and convicilin are potential major allergens from pea". Clinical & Experimental Allergy. 34 (11): 1747–1753. doi:10.1111/j.1365-2222.2004.02085.x. PMID   15544600. S2CID   24690605.
  10. ↑ Krishnan, H B (2001). "Seed Storage Proteins".
  11. ↑ Hirano, Hisashi (2021-05-30). "Basic 7S globulin in plants". Journal of Proteomics. 240: 104209. doi:10.1016/j.jprot.2021.104209. ISSN   1874-3919. PMID   33794343. S2CID   232763820.
  12. ↑ Harris, T; Eagle (1935). "The Immunological Specificity of the Euglobulin and Pseudoglobulin Fractions of Horse and H^man Serum". J Gen Physiol. 19 (2): 383–396. doi:10.1085/jgp.19.2.383. PMC   2141424 . PMID   19872935.


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