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

III. Fat-Soluble Vitamins
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immunodeficiency, dermatosis, anorexia, myopathy, steatitis,
focal interstitial, focal myositis of skeletal muscle,
and periportal mononuclear infiltration in the liver. Signs
of vitamin E deficiency are mostly attributed to membrane
dysfunction as a result of the oxidative degradation of
polyunsaturated membrane phospholipids and disruption
of other critical cellular processes.
Vitamin E can also influence two major signal transduction
pathways centered on protein kinase C and phosphatidylinositol
3-kinase ( Singh and Jialal, 2005 ). Changes in
the activity of these key kinases are associated with changes
in cell proliferation, platelet aggregation, and NADPH-oxidase
activation. Vitamin E status also influences genes that
are involved in the uptake and degradation of tocopherols
and antioxidant defense (e.g., α -tocopherol transfer protein,
cytochrome P450-3A, γ-glutamyl-cysteine synthetase
heavy subunit, and glutathione-S-transferase), genes that are
involved in the modulation of extracellular matrix proteins
(e.g., collagen- α -1 chains and connective tissue growth factor),
genes that are connected to cell adhesion and inflammation
(ICAM-1 integrins and TGF- β ), and genes in the
steroid superfamily (e.g., PPAR- γ ) (Azzi et al., 2004 ).
4 . Evaluation of Vitamin E Status
Tocopherols in biological tissues can be measured by HPLC.
Although the α -tocopherol can readily be separated from
other tocopherols, the separation of the β - and γ-isomers
is difficult. For nutritional assessment of vitamin E, the
current indices are based on changes in total tocopherol
concentrations in plasma and serum. Measurement of
tocopherol concentration in erythrocytes may be an even
better indicator for tissue vitamin E than plasma or serum
levels. The platelet concentration of vitamin E is also a
sensitive measure of vitamin E intake. Moreover, in the
experimental setting the measurement of adipose levels of
tocopherols seems to be a reliable index for assessing longterm
vitamin E status. As in other cells, vitamin E partitions
primarily into the membrane lipid compartments. Thus, the
concentration of vitamin E per adipose tissue mass may
even increase when there is loss of nonmembrane stored triglycerides.
As plasma tocopherol concentration is affected
by lipid concentration, an α -tocopherol/total lipid ratio of
0.6 to 0.8 mg/g of total lipids has been suggested as indicating
adequate nutritional status. Functional tests such as the
erythrocyte hemolysis in the presence of 2% peroxide have
also been used to indicate status ( Traber, 2007 ).
D . Vitamin K
1 . Introduction
In 1929, Henrik Dam reported what was thought first to
be an essential role for cholesterol in the diet of chickens.
He noted that chicks fed diets that had been extracted with
Prothrombin precursor (Glu)
~
|
CH 2
1
|
COOH
VITAMIN K
QUINOL
3
NAD
disulfide
2
NADH
1
2
3
nonpolar solvents to remove sterols developed subdural
and muscular hemorrhages and that blood seemed to clot at
a slower rate. Edward Doisy in the United States did much
of the work that led to the discovery of the structure and
chemical nature of vitamin K. Dam and Doisy shared the
1943 Nobel Prize for medicine for this work. For several
decades, the vitamin K-deficient chick model was the only
method of quantitation of vitamin K in various foods: the
chicks were made vitamin K deficient and subsequently
fed diets with known amounts of vitamin K-containing
food. The extent to which blood coagulation was restored
by the diet was taken as a measure for its vitamin K content.
As this work progressed, it was soon demonstrated
that hemorrhagic disease in chicks could be reversed by
extracts of alfalfa. In the 1940s, it became clear that substances
synthesized by bacteria also could reverse hemorrhagic
symptoms. In addition, it was discovered that
compounds in spoiled clover and grasses seemed to cause
hemorrhagic disorders in animals and serve as antagonist
to vitamin K ( Fig. 23-12 ).
2 . Function and Metabolism
Vitamin K -glutamyl carboxylase
Vitamin K epoxide reductase
Vitamin K reductase
Warfarin
dithiol
O 2 CO 2
VITAMIN K
QUINONE
Dietary sources
Native prothrombin (Gla)
~
|
CH
Warfarin
disulfide
HOOC COOH
VITAMIN K
EPOXIDE
dithiol
FIGURE 23-12 Major components in vitamins K’s role in γ -carboxyglutamyl
residue formation.
With the isolation and identification of vitamin K, work
toward an understanding of mechanisms proceeded,
although not without controversy. At first there was the
problem of reconciling how compounds present in the
sweet clover acted as vitamin K antagonists. A number of
questions were also raised regarding the structural requirements
for vitamin K activity ( Stafford, 2005 ; Suttie, 2007 ).
Now it is appreciated that a number of compounds in
the 1,4-naphaquinone series possess vitamin K activity. For
example, even relatively simple compounds, such as menadione,
possess vitamin K activity. An active phylloquinone
can be synthesized from menadione when combined with
isoprenoids from the cholesterol synthesis pathway. Dietary
2
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