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

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Chapter | 23 Vitamins
results in the strong acidity of ascorbic acid. Enediols
are excellent reducing agents; the reaction usually occurs
in a stepwise fashion with a semiquinone intermediate
( Johnston et al., 2007 ).
For ascorbic acid, this intermediate with monodehydroascorbic
acid disproportionates to ascorbic acid, and dehydroascorbic
acid. Dehydroascorbic acid is not as hydrophilic
as ascorbic acid, because it exists in a deprotonated form.
As such, dehydro of ascorbic acid can move easily across
cell membranes. The dehydro form, however, is easily
cleaved by alkali (e.g., to oxalic acid and threonic acid).
c . Absorption, Tissue Distribution, and Metabolic
Functions
Dietary ascorbic acid is absorbed from the duodenum and
proximal jejunum. Measurable amounts can also cross the
membranes of the mouth and gastric mucosa. Although
some controversy exists regarding the relationship between
ascorbic acid intake and the intestinal absorption of ascorbic
acid, most careful studies indicate that within the physiological
ranges of intake (20 to 400 mg per kilogram of
dry food), 80% to 90% of the vitamin may be absorbed.
With respect to tissue distribution, the highest concentration
of ascorbic acid is found in the adrenal and pituitary
glands followed by the liver, thymus, brain, and pancreas.
In diabetic animals, the ascorbic acid content of tissue is
often depressed, which suggests that factors responding to
hyperglycemic states can compromise ascorbic acid status.
This may be because dehydroascorbic acid uptake is facilitated
by hexose transporters ( Johnston et al., 2007 ; Said,
2004 ). Uptake of reduced ascorbic acid involves a specialized
Na -dependent, carrier-mediated system; egress
of ascorbic acid from enterocytes also utilizes a Na -
dependent carrier system. Regarding cellular retention,
ascorbic acid is maintained in cells by several mechanisms.
Ascorbate reductases maintain L-ascorbic acid in
the reduced form, which prevents passive leakage from
the cell as dehydroascorbic acid. Significant amounts of
ascorbic acid, particularly in fish, may also exist as the
2-sulfate derivative. In rats, about 5% of a labeled dose of
ascorbic acid is recovered in urine as 2-O-methyl ascorbic
acid. Cellular modification of ascorbic acid is important for
compartmentalization or modulation of functional ascorbic
acid levels ( Johnston et al., 2007 ; Wilson 2005 ).
In the neonate, glutathione is important to ascorbate
recycling and regeneration ( Fig. 23-14 ). An argument
can be made for a dietary need for ascorbic acid in some
neonates of species not normally showing a requirement
for ascorbate. For example, the levels of glutathione are
relatively low in neonate rat and mouse tissue. Ascorbate
is oxidized to dehydroascorbic acid, which is easily catabolized,
thus the need for continual replacement.
As a cellular reducing agent, ascorbic acid plays a
number of important roles. It serves as a cofactor for
mixed-function oxidations that result in the incorporation
GLY
GLUCySH
γ-GLU-CySH
Peroxides
(2) GSH GSSG
H 2 O 2
Dehydroascorbate
Degradation
Products
Reductase
NADPH
Glutaredoxin
H 2 O 2
Ascorbate
FIGURE 23-14 Interaction between ascorbic acid and glutathione. The
most important reductant in the cell is glutathione L-(-glutamyl-L-cysteineglycine,
GSH), which is synthesized by a two-step reaction involving
L-glutamyl cysteine synthetase and GSH synthetase. In addition to reducing
equivalents derived from the pentose shunt or hexose monophosphate
shunt pathway via NADPH, reduced ascorbic acid can transfer reducing
equivalents to oxidized glutathione (GSSG) catalyzed by glutaredoxin.
of molecular oxygen into various substrates. Examples
include the hydroxylation of proline in collagen, elastin,
C1q complement, and acetylcholine esterase. Hydroxylases
(monooxygenases) and some P450-dependent hydroxylases
that carry out the hydroxylation of steroids, drugs,
and other xenobiotics utilize ascorbic acid as a reductant.
Moreover, the hydroxylation steps in the biosynthesis of
carnitine, hydroxylation of tyrosine in the formation of
catecholamines, and hydroxylation of proline in collagen
represent other important and essential catalytic functions
of ascorbic acid. Most of the enzymes involved in these
processes are metal-requiring enzymes in which ascorbic
acid’s role is to maintain the metal (usually Cu or Fe) in its
reduced state ( Johnston et al., 2007 ).
d . Requirements and Toxicity
Ascorbate is synthesized by most animals with the exception
of primates, guinea pigs, some snakes, fruit-eating
bats, birds (passerines), and salmonid fish. For these animals,
impaired collagen synthesis is a principal feature
of ascorbate deficiency. Scurvy is characterized by poor
wound healing, impaired bone formation in higher animals,
and kyphosis and scoliosis in fish ( Committee on Animal
Nutrition, 2001a, 2001b ; Subcommittee on Laboratory
Animal Nutrition, Board on Agriculture, National Research
Council, 1995). Connective tissue lesions are primarily a
result of underhydroxylated collagen (at specific prolyl and
lysyl residues) being abnormally susceptible to degradation.
In addition, the inability to deal with metabolic stress
requiring normal adrenal gland function and the reduced