UPTAKE AND STORAGE IN THE LIVER, AND MOBILISATION FROM THE LIVER

Triacylglycerol hydrolysis and apolipoprotein exchange of chylomicrons give rise to the chylomicron remnants which are taken up by the liver (in addition to other tissues). Most of the retinyl esters are delivered in this manner to the liver, and some are taken up by extrahepatic tissues.

In the liver, vitamin A in form of retinyl esters, is first taken up by the hepatocytes and hydrolysed to retinol. Retinol is then bound to retinol binding protein (RBP) in the endoplasmic reticulum, and secreted into the blood or stored in stellate cells. RBP is associated with transtyretin (TTR) in plasma in a 1:1 ratio and possibly assembled with RBP-retinol in the ER. This makes the complex large enough to prevent glomerular filtration, and subsequent loss of retinol through the kidneys. The hepatocytes are the major producers of RBP, but other extrahepatic tissues are also able to make RBP, but to a much lower degree.

A large portion of the secreted retinol is taken up by the perisinusoidal stellate cells where it is esterified and stored as retinyl esters in lipid droplets. The CRBPI and LRAT are important in facilitating and performing esterification of retinol in the stellate cells, since knocking out either of them almost completely abolishes retinyl ester formation.

About 80 % of the body's total retinol and retinyl esters are present in the liver. The vitamin A storage in the liver can last for weeks to months. This large storage and the body’s ability to mobilize retinol, ensures a steady plasma concentration of about 1-2 µM. Retinol recycles between plasma, liver and extrahepatic tissues.