Retinol extrahepatic

Release from the liver When needed, retinol is released from fie liver and transported to extrahepatic tissues by the plasma retax -binding protein (RBP). The retinol-RBP complex attaches to spe cific receptors on the surface of the cells of peripheral tissues, permitting retinol to enter. Many tissues contain a cellular letaiol-binding protein that carries retinol to sites in the nucleus where the vitamin acts in a manner analogous to steroid hormones. 

Several interesting hypotheses resulted from this model (Green et al, 1985). (1) Plasma retinol recycled 12 times before irreversible loss and its turnover rate (nmol/day) was 13 times the disposal rate (24 nmol/day). That is, in support of our previous results (Lewis et al, 1981), an average plasma retinol molecule apparently recycles many times before irreversible utilization. (2) In contrast to the belief that the liver is the sole source of plasma retinol/RBP, our model predicted that 55% of plasma retinol input was from the liver and 45% was from extrahepatic tissues. (3) The model predicted that, in these rats that had marginal liver vitamin A stores and that were in slight negative vitamin A balance, almost half of the whole-... 

FIG. 7. Compartmental model predicted masses and concentrations of retinol and retinyl ester in plasma, liver, and extrahepatic tissue of a healthy adult who ingested a single 73-/imol dose of /S-carotene-dn orally. The Fast turnover liver retinoid (bottom left) and Slow turnover liver retinoid (bottom right) each include the protio and deuterated species. 

The interaction between alcohol and vitamin A is complex. They have overlapping metabolic pathways a similar 2-step process is involved in the metabolism of both alcohol and vitamin A, with alcohol dehydrogenases and acetaldehyde dehydrogenases being implicated in the conversion of vitamin A to retinoic acid. Alcohol appears to act as a competitive inhibitor of vitamin A oxidation. In addition, chronic alcohol intake can induce cytochrome P450 isoenzymes that appear to increase the breakdown of vitamin A (retinol and retinoic acid) into more polar metabolites in the liver, which can cause hepatocyte death. So chronic alcohol consumption may enhance the intrinsic hepatotoxicity of high-dose vitamin A. Alcohol has also been shown to alter retinoid homoeostasis by increasing vitamin A mobilisation from the liver to extrahepatic tissues, which could result in depletion of hepatic stores of vitamin A. ... 

Quadro, L., Blaner, W. 8., Hamberger, L. et al. 2004. The role of extrahepatic retinol binding protein in the mobihzation of retinoid stores. J Lipid Res 45 1975-1982. 

Dietary retinyl esters are hydrolyzed in the intestinal lumen, and the resulting retinol is absorbed into the mucosal cell. Retinol in the mucosal cell (newly absorbed or newly synthesized from carotene) is reesterified with long-chain, mainly saturated fatty acids the retinyl esters, in association with chylomicrons, are then transported via the lymph into the general circulation. After entry into the vascular compartment, chylomicrons are metabolized in extrahepatic tissues by the lipolytic removal of much of the chylomicron triglyceride. The chylomicron remnant thus formed is a smaller and cholesterol-rich particle that contains essentially all the chylomicron retinyl esters and is removed from the circulation almost entirely by the liver. 

The liver plays the major role in the body in the uptake and metabolism of newly absorbed retinol (retinyl esters). Thus, retinyl esters appear to remain almost completely with the hydrophobic core of the chylomicron during its extrahepatic conversion to a remnant particle, and then to be taken up by the liver in association with the chylomicron remnant. A quantitative and detailed study of these processes was reported by Goodman et al. (1965). Chylomicrons containing newly absorbed labeled retinol (93% as retinyl esters) were injected intra-... 

Retinol is delivered to target tissues by holo-RBP, possibly by the very small amount of holo-RBP normally present in the free uncomplexed state. Etelivery of retinol to extrahepatic tissues may involve specific cell-surface receptors for RBP. The apo-RBP that results after delivery of retinol probably has a reduced affinity for TTR and is thus selectively enriched in the free RBP fraction. 

RBP is responsible for the delivery of retinol from the liver to the extrahepatic sites of action of the vitamin. Evidence is available that this delivery process may involve cell-surface receptors for RBP. Thus, studies have been reported that suggest that there are specific cell-surface receptors for RBP on monkey small intestine mucosal cells, on bovine pigment epithelial cells from the eye, and on chicken testicular cell membranes. 

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