Chemistry Reference
In-Depth Information
phospholipids packed together in a characteristic manner with cholesteryl
esters and some specific apolipoproteins (Harrison, 2005; Blomhoff and
Blomhoff, 2006). These lipoprotein complexes are secreted into the lymph
where much of the triacylglycerols are hydrolysed by plasma lipoprotein
lipase, leaving remnants that contain most of the newly formed retinyl ester,
retinol and carotenoids (Harrison, 2005). The chylomicron remnants are
taken up rapidly by the liver and almost quantitatively (50-80%), which is
the main site of storage of total body retinol (retinol plus retinyl esters)
(Biesalski and Nohr, 2004; Blomhoff and Blomhoff, 2006). The carotenoids
do not accumulate in liver cells, but are mobilized as components of very low
density lipoprotein (VLDL) particles that are converted to VLDL remnants
and low-density lipoprotein (LDL) in the circulation (Parker, 1996).
To meet tissue needs for retinoids, the liver secretes retinol bound to an
-globulin, retinol-binding protein (RBP); this serves to maintain the vitamin
in aqueous solution, protects it against oxidation and delivers the vitamin to
target tissues. Approximately 95% of the retinol-RBP is associated (1:1) with
the thyroxine-binding prealbumin, transthyretin (TTR). This complex is
important to prevent urinary loss of retinol bound to the relatively small
RBP (Zanotti and Berni, 2004).
The plasma concentration of retinol-RBP is strictly regulated and main-
tained at about 2 mmol/l, despite fluctuations (varies by
>
15-fold) in daily intake
of vitamin A (Olson, 1984). Only in severe vitamin A deficiency, i.e. when liver
retinyl esters are depleted, is the concentration of plasma retinol-RBPreduced
(Blomhoff and Blomhoff, 2006). Kinetic studies show that each molecule of
retinol circulates several times between plasma and liver before undergoing
irreversible disposal (Green and Green, 2003; Cifelli et al., 2005). In humans,
50 mmol/day (14.3 mg/day) of retinol passes through plasma, compared with
an estimated disposal rate of 4 mmol/day (1.14 mg/day) (Von Reinersdorff et al.,
1998). Therefore, a large portion of retinol taken up by most cell types in the
body is recycled to plasma and only a minor portion is converted to active
metabolites or is degraded. Ross and Zolfaghari (2004) concluded that recycling
provides an ideal means for the liver to sample constantly and adjust the
concentration of retinol available in plasma for peripheral tissues.
The main excretory product of both retinol and retinoic acid is retinoyl
glucuronide, which is secreted in the bile (Bender, 2003). Some products of
side-chain oxidation of retinoic acid are also excreted in the urine. As the
concentration of retinol intake increases, a microsomal cytochrome P
450
-
dependent oxidation process is activated, leading to a number of polar
metabolites, including 4-hydroxyretinol, which is excreted in the urine and
bile. At high intakes, this pathway becomes saturated and excess retinol is
toxic since there is no further capacity for its catabolism and excretion
(Bender, 2003).
