Retinol-binding protein-transthyretin complex

Vitamin A homeostasis was altered in rats that were exposed to 100 mg/kg/day (only tested dose) of PCB 169 in the diet for 77 days (Bank et al. 1989). Effects included significantly decreased hepatic vitamin A, increased renal vitamin A, increased serum retinol, decreased plasma clearance and half-time of injected retinol (i.e., intravenously administered [ Hjretinol-labeled retinol binding protein-transthyretin complex), decreased hepatic and increased renal uptake uptake of injected retinol, and increased urinary and fecal excretion of injected retinol. 

Transthyretin (formerly prealbumin binds T4 and forms a complex with retinol-binding protein)... 

The other major class of extracellular LBPs of mammals is the lipocalins (Flower, 1996). These are approximately 20 kDa, P-sheet-rich proteins, performing functions such as the transport of retinol in plasma or milk, the capture of odorants in olfaction, invertebrate coloration, dispersal of pheromones, and solubilizing the lipids in tears (Flower, 1996). The retinol-binding protein (RBP) of human plasma is found in association with a larger protein, transthyretin, the complex being larger than the kidney threshold and thus not excreted, although the RBP itself may dissociate from the complex to interact with cell surface receptors in the delivery of retinol (Papiz et al., 1986 Sundaram et al., 1998). 

Free retinol is released from the liver as a 1 1 complex of retinol with the 21-kDa retinol-binding protein.k l This protein is normally almost saturated with retinol and is bound to another serum protein, the 127-residue transthyretin (prealburnin).m/n Some of the retinol is oxidized to retinoic acid. 

When vitamin A stores are adequate, the liver secretes retinol bound to retinol-binding protein (RBP) into the circulation to provide tissues with a constant supply of vitamin A. In the circulation, the retinol-RBP complex is found bound to another circulating protein of hepatic origin, transthyretin (TTR). TTR also binds thyroid hormone and consequently plays a role in the transport of both vitamin A and thyroid hormone. The molecular size of the retinol-RBP complex is quite small, and the formation of the... 

Liver Storage and Release of Retinol Tissues can take up retinyl esters from chylomicrons, but most is left in the chylomicron remnants that are taken up into the liver by endocytosis. The retinyl esters are hydrolyzed at the hepatocyte cell membrane, and free retinol is transferred to the rough endoplasmic reticulum, where it binds to apo-RBP. Holo-RBP then migrates through the smooth endoplasmic reticulum to the Golgi and is secreted as a 1 1 complex with the thyroid hormone binding protein, transthyretin (Section 2.2.3). 

Bellovino D, Morimoto T, Tosetti F, and Gaetani S (1996) Retinol binding protein and transthyretin are secreted as a complex formed in the endoplasmic reticulum in HepG2 human hepatocarcinoma cells. Experimental Cell Research 222,77-83. 

Thyroid hormones have a lengthy life-span in the bloodstream — several days — probably because they are bound to proteins in the circulation. More than of T4 and T3 is bound to plasma proteins. These prolerns arc thyroid hormone-binding protein, transthyretin, and albumin. Most of the hormone is carded by thyroid hormone-binding protein. Transthyretin (from thyroid and retinol) occurs in a Irl complex with retinol-binding protein In the bloodstream. This complex serves to prevent the loss of retinol-binding protein, which is a small protein, in the urine. Transthyretin has also been called prealbumin, it binds T4 and not TJ,... 

The retinyl esters are incorporated into chylomicrons, which in turn enter the lymph. Once in the general circula-tion. chylomicrons arc converted into chylomicron remnants, which arc cleared primarily by the liver. As the c.stcrs enter the hepalocytes. they are hydrolyzed. In the endoplasmic reticulum, the retinol is bound to retinol-binding protein (RBP). This cotnplex is released into the blood or transferred to liver stellate cells fur storage. Within the stellate cells, the retinol is bound to CRBP(I) and e.stcnTicd for storage by ARAT and LRAT. Stellate cells contain up to 95% of the liver vitamin A. stores. The RBP-retinol complex released into the general circulation from hepalocytes or stellate cells, in turn, is bound to transthyretin (TTR), which protects retinol from metabolism and renal excretion. ... 

Transthyretin (prealbumin) and retinol-binding protein (RBP) are transport proteins that migrate together as a 1 1 molecular complex. Transthyretin was originally named prealbumin because of its electrophoretic mobility it was renamed in 1981 to reflect its binding and transport of both thyroid hormones (thyroxine and triiodothyronine) and RBP. 

Transthyretin (also known as prealbumin) Liver plasma circulating form is a tetramer composed of four identical monomers. M.W. 55,000 1-2 days N 20-40 mg/dl Mild 10-15 mg/dl Moderate 5-10 mg/dl Severe <5 mg/dl Circulates in plasma in a 1 1 complex with retinol-binding protein, transports thyroxine, has a small body pool, and has a short half-life. Sensitive indicator of protein deficiency and in the improvement with protein refeeding. 

Retinol-binding protein (RBP) Liver M.W. 21,000 10-12 hours N 3.5-9.0 mg/dl Circulates in plasma in 1 1 complex with transthyretin, transports retinol and thyroxine, plasma levels influenced by glomerular filtration rate, retinol and zinc status, considered to be too sensitive and therefore has limited value... 

The first lipocalin whose 3-D structure was solved and refined at high resolution was the human plasma retinol-binding protein (RBP) [22, 23]. RBP acts as a natural transporter of vitamin A (retinol) in the blood of vertebrates. Upon complexation in a hydrophobic cavity with complementary shape, the poorly soluble terpenoid alcohol becomes packaged by the protein and protected from oxidation or double-bond isomerization. RBP is synthesized in the liver and directly loaded with fhe hgand in fhe hepatocyte, where retinol is stored. Furthermore, the holo-RBP forms a structurally defined ternary complex with transthyretin [24], also known as prealbumin. After delivery of the retinol ligand to a target tissue, fhe complex decomposes and fhe monomeric apo-RBP becomes filtered out by fhe kidney and degraded. 

Vitamin A is transported m the plasma as retinol bound to a carrier protein, called retinol-binding protein (RBP), which itself forms a complex with the thyroxine-binding protein, known as transthyretin (TTR). This complex exists in equilibrium with free holo-RBP, which can then interact with a specific cell-surface receptor, thereby inducing the release of its retinol to the target cell. Thus, RBP possesses at least three molecular-recognition properties it binds retinol and it interacts with both TTR and the cell-surface receptor (for reviews, see refs. I and 2). 

Most of the retinol that is delivered to the eye originates in the liver, and is released into the circulation (mainly in the all-trans configuration) bound to an M, 21,000 protein, serum retinol-binding protein (RBP). This protein, which contains no bound lipid or carbohydrate, circulates as a 1 1 complex with transthyretin (TTR, originally prealbumin) (see Chapter 8 for detailed discussion). 

Retinol is released from the liver bound to an a-globulin, retinol-binding protein (RBP) this serves to maintain the vitamin in aqueous solution, protects it against oxidation and also delivers the vitamin to target tissues. RBP is secreted from the liver as a 1 1 complex with the thyroxine-binding prealbumin, transthyretin. This is important to prevent urinary loss of retinol bound to the relatively small RBP, which would otherwise be filtered by the kidney, with a considerable loss of vitamin A from the body. 

Rostom, A. A. Sunde, M. Richardson, S. J. Schreiber, G. Jarvis, S. Bateman, R. Dobson, C. M. Robinson, C. V, Dissection of multi-protein complexes using mass spectrometry subunit interactions in transthyretin and retinol-binding protein complexes. ProteinsStructure Function and Genetics 1998, 3-11. 

Melhus H, Nilsson T, Peterson PA, Rask L (1991) Retinol-binding protein and transthyretin expressed in HeLa cells form a complex in the endoplasmic reticulum in both the absence and the presence of retinol. Exp Cell Res 197 119-124... 

Holven KB, Natarajan V, Gundersen TE, Moskaug J0, Norum KR, Blomhoff R (1997) Secretion of N-(4-hydroxyphenyl) retinamide-retinol-binding protein from liver parenchymal cells evidence for reduced affinity of the complex for transthyretin. Int J Cancer 71 654-659... 

Transthyretin (TTR) A protein complex found in blood that binds both retinol (vitamin A) and thyroxine. 

Brouwer A and van den Berg KJ (1986) Binding of a metabolite of 3,4,3, 4 -tetra-chlorobiphenyl to transthyretin reduces serum vitamin A transport by inhibiting the formation of the protein complex carrying both retinol and thyroxin. Toxicology and Applied Pharmacology 85,301-12. 

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