Thyroxine-binding globulin is a protein that binds the thyroid hormones triiodothyronine (T3) and L-thyroxine (T4) in the body. These play an important role fϋr energy metabolism in mammals.
What is thyroxine-binding globulin?
Thyroxine-binding globulin belongs to the group of globulins, storage and transport proteins, in blood plasma. Globulins are divided into four groups. This subdivision is based on the electrophoretic movement of these proteins during serum protein electrophoresis, a laboratory test of proteins in blood plasma. The proteins are separated by electrical charge. The α1-globulin group includes thyroxine-binding globulin, but also transcortin, for steroid transport, prothrombin, which is involved in blood clotting, and transcobalamin, which binds vitamin B12. In addition, the Gc globulins, which bind vitamin D, bilirubin transporters, and α1-antitrypsin belong to this group of globulins. The α2-globulins consist of the α2-haptoglobin, hemoglobin-binding globulins, plasminogen, α2-macroglobulin, α2-antithrombin, and caeruloplasmin, which transports copper ions in the blood. The β-globulins are involved in the transport of lipids by the β-lipoproteins. In addition, transferrin for iron transport, fibrinogen and hemopexin fϋr hemin binding and transport belong to this group. The γ-globulins consist of the immunoglobulins. These are also known as antibodies and are used for the body’s immune defense.
Function, action, and roles
Thyroxine-binding globulin binds the thyroid hormones triiodothyronine (T3) and L-thyroxine (T4). It serves to store and transport these hormones in the body to the various destinations where these hormones are needed. T3 and T4 are thyroid hormones based on the amino acid tyrosine, which are essential components of energy metabolism. It acts throughout the body and is involved in metabolism, protein biosynthesis, bone marrow growth, and neuron maturation. It also regulates the body’s sensitivity to catecholamines such as epinephrine. Furthermore, thyroxine is involved in fat and carbohydrate metabolism as well as vitamin metabolism. This shows how diverse the functions of thyroxine are and how important it is that it reaches its destination in the body efficiently through the transport protein. In blood plasma, T3 is 99% bound and thyroxine-binding globulins. L-thyroxine is also 99.9% bound to them. Both hormones are present only in small amounts freely, this is then called free hormone. However, thyroxine-binding globulin is not the only protein that carries out the transport of T3 and T4. This transport can also be performed by transthyretin or serum albumin. However, thyroxine-binding globulin has a higher affinity for these thyroid hormones compared to the other two proteins. However, thyroxine-binding globulin is present in human blood only in smaller amounts than transthyretin or serum albumin. It mainly binds and transports T4 in blood plasma and is about 25% saturated with thyroid hormones. This is due to the relatively small amount of thyroid hormones in the blood. These transport proteins protect the hydrophobic thyroid hormone from its aqueous environment in the blood. Thyroxine-binding globulin also belongs to the serpins, a family of serine protease inhibitors. Proteases are proteins that can break down other proteins into their component parts. Thyroid hormone is released from globulin by being separated from it through active cleavage. This type of binding between thyroid hormone and globulin is called reversible because it can be reversed by it through active cleavage.
Formation, occurrence, properties, and optimal values
Thyroxine-binding globulin is produced mainly in the liver. It is a 54-kDa protein that is first synthesized as a polypeptide. This is followed by maturation and folding of the protein to make it functional. The concentration of thyroxine-binding globulin is about 260 nmol/l in an adult. However, the concentration of this globulin depends on various factors. The concentration can be increased by pregnancy or by taking contraceptive drugs or estrogen preparations.Various other drugs are known to increase the concentration of thyroxine-binding globulin, such as tamoxifen, which is used in the treatment of breast cancer opium-containing drugs. In addition, the concentration may also be increased by hepatitis or even genetically. A decrease in thyroxine-binding globulin concentration can be produced by other drugs such as glucocorticoids or androgens. In addition, nephrotic syndrome or likewise genetic causes have a decreasing effect on the concentration of this globulin.
Diseases and disorders
A relatively rare disorder is chronic deficiency of thyroxine-binding globulin. A distinction is made between complete deficiency of thyroxine-binding globulin and partial deficiency of this globulin. The complete deficiency results in a total loss of this globulin, the partial deficiency results from a reduction in the amount of globulin or from a change in the structure of the protein. This change in the protein structure may have genetic causes. Due to these structural changes, the globulin is no longer able to bind and transport the thyroid hormone. The function of the thyroid gland is not affected by this disease. However, these disorders do not cause any health problems because this globulin is not the only protein that can bind and transport thyroid hormone.
