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chapter38
Vitamin Metabolism
(a)
Photoactivated Rhodopsin (R*)
ATP
Rhodopsin kinase
A D P
Phosphorylated - R ( P - R)
Arrestin
P-R-Arrestin
—
t—
►
Arrestin
-1 1 -C is retinal
Rhodopsin-11-Cis retinal
(b)
H o
Intrinsic
?
G TPase
Pi
J l
Active PD E -
©
v
►
Inactive P D E (PD E-I)
creatine and phosphocreatine (an important energy source)
by inhibiting the enzyme glycine transaminidase. The sec-
ond is the inhibitory effect of ornithine on A'-pyrroline-
5-carboxylate synthase preventing formation of proline
(Chapter 17). Local proline synthesis in the retina is re-
quired because of the lack of entry of proline from plasma.
Treatment of gyrate atrophy represents an attempt to re-
duce the concentration of ornithine by administering phar-
macological doses of pyridoxal phosphate (vitamin B6),
which is a cofactor of OAT, restricting dietary intake of
arginine, which is a precursor of ornithine, and augment-
ing renal loss of ornithine by inhibiting the renal dibasic
amino acid transport using lysine or the nonmetaboliz-
able a-aminoisobutyric acid. In some patients, therapeu-
tic benefits also have been obtained by supplementing the
decreased end products, creatine and proline.
(o)
G TP
Guanylyl Cyclase
(reopening of the
cation channels)
Vitamin E
Nutrition and Chemistry
Low Car2*
FIGURE 38-10
Recovery and the restoration to dark state in the rod and cone cells require
three sets of reactions, a, b, and c. The light-induced lowering of cytosolic
Ca2+ levels (see Figure 38-9) initiates the process of adaptation to dark
(see text for details).
Pj,
Inorganic phosphate; ©, stimulation;
I,
inhibitory
subunit of phosphodiesterase.
Vitamin E was crystallized and its structure determined
in 1936. Eight plant vitamers are known (Figure 38-11),
the most abundant and active being a
-tocopherol.
Vitamin E vitamers are viscous, light yellow oils that
are heat stable but readily degraded by oxygen or ul-
traviolet light. Principal sources are the vegetable oils,
(Figure 38-10). The GTP bound to
a
subunit is hydrolyzed
by the intrinsic GTPase activity of
a
subunit, followed by
its reassociation with T^y to form inactive T„.GDP./
3
y • The
formation of T„ GDP./iy results in the reversion of PDE to its
inactive state. Photoactivated rhodopsin is inactivated by
phosphorylation at multiple serine and threonine residues
and is catalyzed by rhodopsin kinase and binding of an
inhibitory protein known as arrestin. Low Ca2+ levels and
recoverin stimulate rhodopsin kinase activity. Prestimu-
lus cGMP levels are attained through the activation of
guanylyl cyclase by low Ca2+ levels, which converts GTP
to cGMP.
A disorder
hyperornithinemia
of the retina and choroid
with gyrate atrophy and progressive degeneration is due to
the deficiency of the enzyme ornithine-))-ami notransferase
(OAT). OAT deficiency is inherited as an autosomal re-
cessive disorder and illustrates the metabolic importance
of ornithine, a nonprotein amino acid (Chapter 17). Or-
nithine participates either as a substrate or a product of
five enzymatic reactions. Two biochemical mechanisms
have been proposed to explain the pathophysiology of gy-
rate atrophy of the choroid and the retina. One is that a
high ornithine concentration causes reduced formation of
Tocopherol
Alpha-
Tocotrienol
Alpha-
a
— CH ,
B ,
— CH,
B ,
— CH,
Beta-
Beta-
— CH,
— H
0
1
Gam m a-
G am m a-
— H
— CH ,
— CH,
Delta-
D elta-
— H
— H
- C H
FIGURE 38-11
Structures of naturally occurring plant compounds having vitamin E
activity. The nucleus in each is
6
-hydroxychroman. Attachment of a
saturated 16-carbon chain produces the tocopherols; the tocotrienols have a
16-carbon unsaturated chain. Both groups are optically active. The
tocotrienols have one chiral center at carbon
2
, while the tocopherols have
three, at carbons
2
, 4', and
8
'. Tocol is a tocopherol in which R i, R
2
, and
R
3
are all hydrogen atoms. The tocopherols can be viewed as methylated
tocols.
