DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

A
CH 3
CH 3
C 7 10 15
1 H 2 C 6 C CH CH C CH CH CH C CH CH
CH 3
CH CH 3 3 CH 3
C
CH CH C CH CH CH C CH CH C CH 2
H 2 C 3 5C
C
H 2
CH 3 CH3
CH 2 OH
CH 3
β-CAROTENE
H 3 C
C
CH 2
C
H 2
B
ALL-trans-RETINOL
OH
CH 2 OH
ALL-trans-14-HYDROXYRETRORETINOL
9-cis-RETINOIC ACID
COOH
CHO
ALL-trans-RETINAL
11-cis-RETINAL
CHO
COOH
ALL-trans-RETINOIC ACID
13-cis-RETINAL
CHO
COOH
COOH
ALL-trans-3, 4-DIDEHYDRORETINOIC ACID
13-cis-RETINOIC ACID
Figure 64–7. A. Structural formula for β-carotene. B. Structural formulas for the vitamin A family of retinoids.
Physiological Functions and Pharmacological Actions. Vitamin A
plays an essential role in the function of the retina, is necessary for
growth and differentiation of epithelial tissue, and is required for
growth of bone, reproduction, and embryonic development. Together
with certain carotenoids, vitamin A enhances immune function,
reduces the consequences of some infectious diseases, and may protect
against the development of certain malignancies. As a result,
there is considerable interest in the pharmacological use of retinoids
for cancer prophylaxis and for treating various premalignant conditions.
Because of the effects of vitamin A on epithelial tissues,
retinoids and their analogs are used to treat a number of skin diseases,
including some of the consequences of aging and prolonged
exposure to the sun (see Chapter 65).
The functions of vitamin A are mediated by different forms
of the molecule. In vision, the functional vitamin is retinal. Retinoic
acid appears to be the active form in functions associated with
growth, differentiation, and transformation.
Retinal and the Visual Cycle. Vitamin A deficiency interferes with
vision in dim light, a condition known as night blindness (nyctalopia).
Photoreception is accomplished by two types of specialized
retinal cells, termed rods and cones. Rods are especially sensitive to
light of low intensity; cones act as receptors of high-intensity light
and are responsible for color vision. The initial step is the absorption
of light by a chromophore attached to the receptor protein. The
chromophore of both rods and cones is 11-cis-retinal. The holoreceptor
in rods is termed rhodopsin—a combination of the protein
opsin and 11-cis-retinal attached as a prosthetic group. The three
different types of cone cells (red, green, and blue) contain individual,
related photoreceptor proteins and respond optimally to light of
different wavelengths.
In the synthesis of rhodopsin, 11-cis-retinol is converted to
11-cis-retinal in a reversible reaction that requires pyridine
nucleotides. 11-cis-Retinal then combines with the ε amino group of
a specific lysine residue in opsin to form rhodopsin. Most rhodopsin
is located in the membranes of the discs situated in the outer
segments of the rods. The protein has seven membrane-spanning
domains, a characteristic shared by all receptors whose functions are
transduced via G proteins.