section 38.1
Fat-Soluble Vitamins
905
(trimethyl-
cyclohexenyl)
ring
FIG U RE 38-1
Chemical structure of all
-tra n s
retinol (vitamin Ai), the most active form
of vitamin A. Oxidation of C
15
to an aldehyde or an acid produces,
respectively, retinaldehyde (retinal) and retinoic acid. The cis-trans
isomerization of the double bond between Ci
1
and C
12
occurs during
functioning of retinaldehyde in vision.
naturally occurring retinoid is all
-trans
retinol, also called
vitamin A (Figure 38-1). The /f-ionone ring is required
for biological activity. Vitamin Ai exists free or as retinyl
esters of fatty acids (primarily palmitic acid) in foods of
animal origin, including eggs, butter, cod liver oil, and the
livers of other vertebrates. In most of the dietary retinol,
the four double bonds of the side chain are in the trans
configuration. They are readily oxidized by atmospheric
oxygen, inactivating the vitamin. They can be protected
by antioxidants such as vitamin E.
Several provitamins are present in yellow and dark
green leafy vegetables and fruits, such as carrots, man-
goes, apricots, collard greens, and broccoli. They are col-
lectively known as the carotenoid pigments or
carotenes.
The most widely occurring and biologically active is
/1-carotene (Figure 38-2). Other nutritionally important
carotenoid pigments are cryptoxanthine, a yellow pigment
found in corn, and
a-
and /-carotenes. Other carotenoids,
such as lycopene the red pigment of tomatoes, and xan-
thophyll, lack the /3-ionone ring essential for vitamin A
activity.
Absorption, Transport, and Metabolism
Retinyl esters
are hydrolyzed in the intestinal lumen
by pancreatic carboxylic ester hydrolase, which also
hydrolyzes cholesteryl esters. In mucosal cells,
retinol
is reesterified, mostly with long-chain fatty acids, by
acyl-CoA: retinol acyltransferase. The retinyl esters are
incorporated into chylomicron particles and secreted into
the lacteals. In humans and rats, 50% of the retinol is
esterified with palmitic acid, 25% with stearic acid, and
smaller amounts with linoleic and oleic acids. These es-
ters are eventually taken up by the liver in chylomicron
remnants. /
6
-Carotene is cleaved in the intestinal mucosa
to two molecules of retinaldehyde by /f-carotene-15,15'-
dioxygenase, a soluble enzyme. Other provitamins are also
activated upon cleavage by this enzyme. Retinaldehyde is
then reduced to retinol by retinaldehyde reductase, using
either NADH or NADPH.
In the liver, retinyl esters are hydrolyzed and reesteri-
fied. More than 95% of hepatic retinol is present as esters
of long-chain fatty acids, primarily palmitate. In an adult
receiving the RDA of vitamin A, a year’s supply or more
may be stored in the liver.
More than 90% of the body’s supply of vitamin A is
stored in the liver. The hepatic parenchymal cells are in-
volved in its uptake, storage, and metabolism. Retinyl es-
ters are transferred to hepatic fat-storing cells (also called
Ito cells or lipocytes) from the parenchymal cells. The
capacity of these fat-storing cells may determine when
vitamin A toxicosis becomes symptomatic. During the de-
velopment of hepatic fibrosis (e.g., in alcoholic liver dis-
ease), vitamin A stores in Ito cells disappear and the cells
differentiate to myofibroblasts. These cells appear to be
the ones responsible for the increased collagen synthesis
seen in fibrotic and cirrhotic livers.
Retinol is released from the liver and transported in
plasma bound to
retinol-binding protein
(RBP), which
is synthesized by hepatic parenchymal cells. Less than
5% circulates as retinyl esters. Retinol-binding pro-
tein from human plasma is a monomeric polypeptide
(M.W. 21,000), which has a single binding site. Transfer
of retinol into cells may be mediated by cell surface re-
ceptors that specifically recognize RBP. After binding and
releasing its vitamin A, RBP appears to have decreased
affinity for prealbumin (see below) and is rapidly filtered
by the kidney and degraded or excreted.
The retinol-RBP complex circulates as a 1:1 complex
with prealbumin (
transthyretin;
M.W. 55,000), which
FIG U RE 38-2
Structure of all
-tra n s
/3-carotene.
