Please note these web pages are part of an assignment for a graduate course in Advanced Biochemistry and Molecular Biology BCMB8010 at the University of Georgia. Please direct questions to Matthew Taylor at vinco@uga.edu
Thyroxine Complexed with Human Serum Albumin
Abstract
Thyroxine, or 3,3',5,5' tetraiodothyronine (T4) is a hormone produced by the thyroid gland. In the T4 form, the hormone is not very active, requiring 5' monodeiodination to 3,3',5 triiodothyronine (T3) for full activity. T3 is involved in a number of regulatory roles in the body. One role that is receiving increasing attention is its involvement in the regulation of neural development in fetal brain development, and the capability of several environmental contaminants to interfere with this regulation. T4 can also be further inactivated by monodeiodination into reverse T3 (3,3',5' triiodothyronine) also known as rT3(1-3). The iodothyronines are collectively known as Thyroid Hormones, or TH.
While the thyroid does directly secrete a small amount of T3, the primary output is in the form of T4. Most of the physiological T3 comes from peripheral tissues expressing one or more of the iodothyronine deiodinases. During the transport of T4 to the peripheral tissues, it is complexed to several serum proteins. In humans, about 3/4 of it is bound to thyroxine binding globulin (TBG), around 15% is complexed with transthyretin (TTR), and most of the remainder associates with serum albumin. Together, these proteins bind more than 99% of circulating T4. The association between T4 and human serum albumin (HSA) is shown in several PDB structures[1hk1-1hk5](2,3,5).
Albumin is involved in binding many bioactive molecules other than T4, using varying regions of the Albumin molecule. It appears that the binding of T4 to albumin is localized to subdomains IIA and IIIA, which are also involved in binding fatty acids(2). In the remainder of this report, the activity of T3 and T4 will be discussed further, as will the interaction between T4 and Human Serum Albumin.
Links
References
1- Visser et. al.: Kinetic evidence suggesting two mechanisms for iodothyronine 5' deiodination in rat cerebral cortex. Proc. Natl. Acad. Sci. USA. Vol. 79. pp5080-5084, (1982)
2- Petitpas et. al.: Structural Basis of Albumin-Thyroxine Interactions and Familial Dysalbuminemic Hyperthyroxinemia. Proc.Nat.Acad.Sci.USA vol. 100 pp. 6440 (2003) Here
3- Zoeller, R. T., Crofton, K. M.: Thyroid Hormone Action in Fetal Brain Development and Potential for Disruption by Environmental Chemicals. NeuroToxicology vol. 21 pp. 953-946 (2000)
4- NCBI Entrez Gene – Homo Sapiens Albumin: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=213 Updated 1 Nov 2004.
5- Whittem, E.: Studies of the Physiological Significance of the Interaction Between Thyroid Hormone and its Binding Proteins. Ph.D. Diss., University of Georgia, 1991.