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

III. Fat-Soluble Vitamins
707
containing rancid lard, unless they were supplemented
with lettuce or whole wheat. Later it was found that germ
oils, particularly wheat germ oil, contained an active
principle that seemed responsible for improving reproductive
performance. These early studies provided yet
another function for a fat-soluble substance. By the early
1930s, it was recognized that this substance was a factor
that differed from vitamin A or vitamin D. The compound
was designated as vitamin E by Barnett Sure and later as
α-tocopherol from the Greek word “ tokos ” meaning childbirth
or reproduction. By 1940, a number of compounds in
the tocopherol family were identified and purified. With
elucidation of tocopherol structures and eventual chemical
synthesis ( Fig. 23-10 ), studies quickly followed that demonstrated
embryonic failure resulted from vitamin E deficiency.
Pappenheimer, Olcott, Martill, and others observed
that muscle degeneration was also a common deficiency
symptom and that vitamin E seemed to function as an
antioxidant. Next, other signs and symptoms were identified,
including oxidative diathesis and encephalomalacia
in chickens. In addition to these signs, liver necrosis and
hemolytic anemias were observed in vitamin E-deficient
animals ( Traber, 2007 ).
2 . Chemistry, Metabolism, and Sources
The principal sources of tocopherols are plant oils.
Tocopherols are unique because they act primarily at a
chemical level as antioxidants, although other possible roles
in cell signaling have been described. Primarily, vitamin E
protects unsaturated fatty acids found in the phospholipids
of cell membranes. The quinone moiety of tocopherols is
capable of quenching free radicals, such as the free radical
of hydrogen (H • ), superoxide radicals (O 2
• ), hydroxyl
radicals (OH • ), and other lipid-derived radical species
(LOO • ). Vitamin E in the course of its action is sacrificed
in acting as a free-radical scavenger. Vitamin E is very
reactive and is in effect sacrificed thus inhibiting the formation
of lipid-derived oxidation products ( Traber, 2007 ).
Cell membranes contain vitamin E at a concentration
of approximately 1 mg per 5 to 10 g of lipid membrane; a
concentration sufficient to retard membrane lipid oxidation.
Membrane lipids are constantly engaged in the process
of turnover and repair. By prolonging the initiation
time before a free-radical chain reactions occurs, vitamin E
gives cells time to replace damaged membrane lipids
through the process of normal cell turnover.
With regard to absorption and transport, tocopherols
first must partition into the intestinal micelles and are
absorbed with other dietary lipids. Following absorption,
vitamin E is transferred into the lymph associated with chylomicrons
and intestinally derived VLDL particles, similar
to other fat-soluble vitamins. Vitamin E is cleared from
chylomicrons and VLDL by the lung and the liver. From
the liver, most of the vitamin E is found in association with
VLDL and LDL particles. For example, there is preference
for the α -tocopherol form of vitamin E. More specifically,
tocopherol-binding proteins favor the retention of the most
potent vitamin E homologue, RRR- α -tocopherol. The LDL
particles contain the highest concentration of vitamin E.
This is important in that high concentrations of vitamin E
protect the LDL particle from oxidation. It is currently proposed
that oxidized LDL particles are important mediators
of vascular disease.
HO
7
HO
7
5
8
5
8
Tocopherol
O CH3
CH 3 CH 3 CH 3
Position
of
methyl groups
allylic
R
H H
H H H
alkyl
5,7,8 =
5,8 =
7,8 =
8 =
O CH3
CH 3 CH 3 CH 3
X • X-H
L-H
• O
T•
Tocotrienol
L•
bis-allylic O 2
H H
R
H H H
LOOH
O
HO
Isomer
designations
LOO •
C 16 H O
33 C16 H
TH
33
O
I 2T• + H + TH + T + +O
R
HO
O
R
II T + + H +H +
2 O [
TQ O
O
OH
R
O
O
+H III T• + LOO •
8-HT
+
O R
OOL
IV
8-HT + H +
[
T + + LOOH
FIGURE 23-10 Vitamin E metabolism. The two principal forms of
vitamin E are shown, tocopherol and tocotrienol. Methyl groups are found
at the 5, 6, and/or 8 position, which may modulate antioxidant potency.
Tocopherol is the most potent of the various forms of vitamin E in biological
systems. Some of the mechanisms involving free-radical quenching
are also shown. Vitamin E is particularly important in quenching free radicals
that are generated from allelic and bis allelic nonconjugated bonds
found in membrane polyunsaturated lipids. Resolutions of the vitamin
radical and other intermediates are shown in steps I and IV,