Retinol-binding protein kidneys

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). 

Studies of renal function in stainless steel welders, whose exposure is mainly to chromium(VI) compounds, were negative. Stainless steel welders had significantly increased (p<0.001) levels of urinary chromium, increased clearance of chromium, and increased serum creatinine compared with controls, but no differences were found in the levels of retinol binding protein, p2-microglobulin or other indices of kidney damage (Verschoor et al. 1988). Similar negative results were found in another group of stainless steel welders (Littorin et al. 1984). 

In the intestinal mucosal cells, /3-carotene is cleaved via an oxygenase (an enzyme that introduces molecular 02 into organic compounds) to frans-retinal (aldehyde form of trans-retinol, as shown in Table 6.2), which in turn is reduced to frans-retinol, vitamin Av Retinol is then esterified with a fatty acid, becomes incorporated into chylomicrons, and eventually enters the liver, where it is stored in the ester form until it is required elsewhere in the organism. The ester is then hydrolyzed, and vitamin Ax is transported to its target tissue bound to retinol-binding protein (RBP). Since RBP has a molecular weight of only 20,000 and would be easily cleared by the kidneys, it is associated in the bloodstream with another plasma protein, prealbumin. 

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. 

A. Specific levels. Whole-blood Cd levels may confirm the exposure normal levels are less than 1 mcg/L. Very little Cd is excreted in the urine, until binding of Cd in the kidney is exceeded and renal damage occurs. Urine Cd values are normally less than 1 mcg/g of creatinine. Measures of tubular microproteinuria (beta-microglobulin, retinol-binding protein, albumin, and metallothionein) are used to monitor the early and toxic effects of Cd on the kidney. 

Henze, A., Frey, S. K., Reila, J. et al. 2008. Evidence that kidney function but not type 2 diabetes determines retinol-binding protein 4 serum levels. Diabetes 57 3323-3326. 

Raila, J., Henze, A., Spranger, J. et al. 2007. Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients. Kidney Inti 72 505-511. 

Retinol is nearly always present in the food in the form of esters which are hydrolysed in the lumen of the intestine. The retinol released is quite readily absorbed into the mucosal cells where it is re-esterified, chiefly with palmitic acid. The retinyl esters are then transported via the lymphatic system into the portal circulation from which they are removed and stored in the liver. Release of the vitamin from the liver depends on the production by the liver of a special retinolbinding protein (RBP). Production of the retinol-binding protein may be disturbed in diseases of the liver or kidneys or in protein/energy malnutrition. In such circumstances retinol cannot be mobilized from the stores and a secondary deficiency may result. Thus it can be seen that the level of retinol in the general circulation is normally highly regulated and is more or less independent of the body s reserves. 

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. 

In the blood, vitamin A esters are transported in association with a retinol-binding protein, whereas the carotenoids are associated with the lipid-bearing protein. Storage of vitamin A is largely in the liver, but small amounts are also stored in the lungs, body fat, and kidneys. The amount of body storage of vitamin A tends to increase with age, but of course this depends on the quantity in the diet and the amount absorbed. It is estimated that a normal adult may store sufficient vitamin A in his/her liver to meet the needs for4to 12 months. Infants and children do not build up such reserves hence, they are much more susceptible to deficiencies. 

Rosales FJ, Ritter SJ, Zolfaghari R, Smith JE, Ross AC (1996) Effects of acute inflanmiation on plasma retinol, retinol-binding protein, and its mRNA in the liver and kidneys of vitamin A-sufficient rats. J Lipid Res 37 962-971... 

Whitman MM, Hamish DC, Soprano KJ, Soprano DR (1990) Retinol-binding protein mRNA is induced by estrogen in the kidney but not the liver. J Lipid Res 31 1483-1490... 

After chronic exposure, cadmium accumulates in the human body and causes kidney diseases, especially lesions of proximal tubular cells. A tubular proteinuria causes an increase in urinary excretion of microproteins. Excretions of retinol binding protein (RBP), (32-microglobulin ((32-M), and a 1-microglobulin are validated biomarkers for analyzing cadmium effects. For this purpose, immunological procedures such as ELISA, and radio- and latex-immunoassays are used. 

Retinoic acid may either enter the target cell from the circulation or may be formed intraceUularly by oxidation of retinol. A number of tissues - but not muscle, kidneys, small intestines, liver, lungs, or spleen - have a cellular retinoic acid binding protein (CRABP) that is distinct from CRBP. Testis and... 

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