Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

III. Fat-Soluble Vitamins
699
Carotenoids
-Carotene
Retinol
Retinyl
Esters
9,10-Oxygenase
15,15’-Dioxygenase
REH
-apo-10’
carotenal
RETINAL + RETINAL
RolDH
SDR
RETINOL
LRAT
REH
Retinyl
Esters
RalDH
-Carotene
RETINOIC ACID
Chylomicrons
Blood
FIGURE 23-4 Absorption and cellular metabolism of carotenoids and retinoids. In the intestinal mucosal cell, some carotenoids are oxidized to both
carotenals and retinals. Retinal can be reduced by alcohol dehydrogenases (RolDH) to retinol and re-esterified by lethichin retinol acyl transferase
(LRAT). Retinol and associated esters are then incorporated into chylomicra, which are released into the lymph. Retinol can also be released from
retinyl esters by action of retinyl ester hydrolase (REH). Moreover, retinol can be oxidized to retinal by short-chain dehydrogenases/reductases (SDR).
Retinoic acid is formed from retinal by the action of retinal dehydrogenase (RalDH). Retinoic acid is sufficiently polar so that movement is directed
to plasma . In contrast, owing to their nonpolar nature, given carotenoid pigments and retinyl esters are partitioned into chylomicrons for delivery into
lymph. Retinol transport and carotenoid transport differ. ROL enters intestinal cells by diffusion and effluxes in part by a basolateral transporter in the
ABCA1 transport family of protein transporters. Carotenoid uptake is mediated by the apical transporter SR-B1, and carotenoid efflux occurs exclusively
via secretion in CM.
Lymph
absorbed (less than 10%), because of the low digestibility
of chloroplasts and release of carotenoids.
In the intestinal mucosal cell, some carotenoids are
oxidized to both carotenals and retinals ( Fig. 23-4 ). Most
of the retinal is next reduced by alcohol dehydrogenases to
retinol and re-esterified. Retinol and associated esters are
then incorporated into chylomicra, which are released into
the lymph.
Chylomicra particles in lymph are carried to the liver
where about 75% of the retinol-derived products are
cleared in most animals. In liver, there is active exchange
of retinyl and other retinoids between stellate (also known
as Ito cells) and parenchyma cells. To buffer such cells
from an excess of vitamin A, it may be “ stored ” in lipid
vacuoles. The storage form is as retinyl esters, where retinyl
palmitate is usually the most predominant form.
As the body needs vitamin A, retinyl ester in the liver
is hydrolyzed and released as retinol bound to retinolbinding
protein (RBP), which binds one molecule of vitamin
A as retinol per molecule of RBP ( Fig. 23-5 ). When
released into circulation, RBP exists as a complex not only
with vitamin A, but also with another protein, transthyretin,
which binds thyroxin. The RBP and the transthyretin
complex transport not only vitamin A, but also thyroxin to
targeted cells. The primary target cells for vitamin A are
epithelial in nature (e.g., fetal epidermal cells, the cells of
the gastrointestinal mucosa, the reproductive tract, pulmonary
secretary cells, and the salivary gland) ( Debier and
Larondelle, 2005 ; Harrison, 2005 ).
In regard to uptake and entry into targeted cells, such
as epithelial cells, the exact role of RBP at the cell surface
is unclear. The association constant (K a ) between retinol
and the transthyretin-RBP complex is relatively low,
approximately 10 6 M/l. For example, this association constant
is about the same as that for the binding of retinol to
other proteins (e.g., albumin), which does not imply a high
degree of specificity. In cell cultures, RBP is not essential
for retinol uptake. However, the interaction of retinol
within RBP’s hydrophobic binding domain protects retinal
from oxidation. The complex is also not cleared by the
kidney, which helps to sustain retinol levels in circulation
( Harrison, 2005 ).
Inside the targeted cells, vitamin A, as retinol, interacts
with cellular-binding proteins that function to control
its subsequent metabolism (e.g., oxidation to retinal and
to retinoic acid). Retinal metabolites do not exist “ free ” in