The Three Thyroxine-Binding Proteins in Rat Serum: Binding Capacities and Effects of Binding Inhibitors
TL;DR: Effects of competitive inhibitors of T4 binding on the prealbumin, as well as on albumin and RTBG, indicate that the T4 sites on the 3 proteins are qualitatively distinct in a pattern similar to that of primates.
Abstract: Polyacrylamide gel electrophoresis shows radiothyroxine added to rat serum is distributed among 3 proteins: a slow-migrating prealbumin (carrying 55% of tracer T4), albumin (15%) and a postalbumin (18%). This tracer pattern is qualitatively similar to that in human serum. Quantitatively, however, the prealbumin is the principal carrier in rat serum, whereas a postalbumin (thyroxine-binding globulin, TBG) is the major carrier in human serum. Rat postalbumin (R-TBG) T4-binding capacity is about 2 5g/100 ml, measured at a T4 concentration in serum of 25 5g/100 ml. Rat prealbumin (RTBPA)- binding capacity determined at a T4 level of 200 5g/100 ml is about 140 5g/100 ml. Effects of competitive inhibitors of T4 binding on the prealbumin, as well as on albumin and RTBG, indicate that the T4 sites on the 3 proteins are qualitatively distinct in a pattern similar to that of primates. Prealbumin has not been generally recognized as the major plasma carrier of T4 in the rat, presumably because the electrophoretic mo...
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TL;DR: These findings reflect the facts that RBP is produced in the liver and mainly catabolized in the kidneys, and delivery of retinol to extra-hepatic tissues appears to involve specific cell surface receptors for RBP.
Abstract: Vitamin A is mobilized from liver stores and transported in plasma in the form of the lipid alcohol retinol, bound to a specific transport protein, retinol-binding protein (RBP). A great deal is known about the chemical structure, metabolism, and biological roles of RBP. RBP is a single polypeptide chain with molecular weight close to 20,000. RBP interacts strongly with plasma prealbumin, and normally circulates in plasma as a 1:1 molar RBP-prealbumin complex. Both the primary and the tertiary structure of prealbumin are known, and the primary structure of RBP has recently been reported. Much information is available about the protein-protein and protein-ligand interactions that are involved in this transport system. Many clinical studies have examined the effects of a variety of diseases on the plasma levels of RBP and prealbumin in humans. Plasma RBP levels are low in patients with liver disease and are high in patients with chronic renal disease. These findings reflect the facts that RBP is produced in the liver and mainly catabolized in the kidneys. Delivery of retinol to extra-hepatic tissues appears to involve specific cell surface receptors for RBP. Vitamin A mobilization from the liver, and delivery to peripheral tissues, is highly regulated by factors that control the rates of RBP production and secretion. Retinol deficiency specifically blocks the secretion of RBP, so that plasma RBP levels fall and liver RBP levels rise. Injection of retinol into vitamin A-deficient rats stimulates the rapid secretion of RBP from the liver into the plasma. The cellular and molecular mechanisms that mediate these phenomena are under investigation. Elucidation of these mechanisms should help define the basic mechanisms that control the mobilization, transport, and delivery of vitamin A.
417 citations
01 Jan 1984
TL;DR: This chapter focuses on the plasma retinol-binding protein (RBP) and describes the structure and chemistry, biochemistry, and metabolism of RBP.
Abstract: Publisher Summary
This chapter focuses on the plasma retinol-binding protein (RBP) and describes the structure and chemistry, biochemistry, and metabolism of RBP. Vitamin A is transported normally in postabsorptive plasma as the lipid alcohol retinol bound to a specific transport protein plasma RBP. Human RBP is a single polypeptide chain with a molecular weight close to 21,000, α1-mobility on electrophoresis, and a single binding site for one molecule of retinol. In plasma, most of RBP normally circulates as the retinol-RBP complex. Vitamin A is mobilized from the liver and is delivered to peripheral target tissues as the retinol-RBP complex. Retinol mobilization and delivery are highly regulated processes that are particularly controlled by processes that regulate the rates of synthesis and secretion of RBP by the liver. Solutions of the retinol-RBP complex are highly fluorescent. The RBP molecule is a single polypeptide chain of about 180–185 amino acid residues containing three intramolecular disulfide bonds. RBP is cleaved by cyanogen bromide into five fragments; of these, the carboxy-terminal fragment represents slightly more than half the molecule.
236 citations
TL;DR: By synthesizing an important hormone carrier protein, the choroid plexus may be an important link in the chemical communication between the central nervous system and the bloodstream.
188 citations
TL;DR: The results obtained suggest very active synthesis of prealbumin in choroid plexus, which would be an important link in the transport of thyroid hormones from the blood to the brain via the cerebrospinal fluid.
184 citations
TL;DR: A model is proposed for Thyroxine transport from the bloodstream into cerebrospinal fluid based on partitioning of thyroxine between choroid plexus and surrounding fluids and binding of thyoxine to transthyretin newly synthesized and secreted by choroids plexi.
177 citations