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

IV. Water-Soluble Vitamins
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are distinguished because of their importance to carbohydrate,
amino acid, and acyl and acetyl transport, respectively.
Biotin, folic acid, and vitamin B 12 (cobalamin) will
be discussed in relationship to their roles in single carbon
metabolism. Several vitamin-like compounds will also be
described. These compounds are products derived from
carbohydrate, amino acid, or fatty acid metabolic pathways
and primarily perform specialized transport functions
or are associated with signal transduction mediators in
cells. A nutritional case can be made that in some animal
species, these compounds have important “ conditional ”
requirements, and developmental periods may be identified
in which a dietary source is required to maintain balance.
A . Vitamins Important to Redox: Ascorbic
Acid, Niacin, and Riboflavin
1 . Ascorbic Acid
a . Introduction
Ascorbic acid functions primarily as a cofactor for microsomal
monooxygenases (hydroxylases) and oxidases. In
most animals, ascorbic acid is synthesized from glucose in
the liver or kidney ( Fig. 23-13 ). In some animals, however,
a deficiency of gulonolactone oxidase, a last step in ascorbic
acid synthesis, results in the need for a dietary source. The
enzymes for ascorbic acid production in the cold-blooded
vertebrates (fishes, amphibians, and reptiles) are located in
the kidneys. Present-day birds, whose ancestors appeared
about the same time as the mammals, have a kidney-liver
transition. The older order of present-day birds, such as the
ducks, pigeons, and hawks, synthesize ascorbic acid in their
kidneys, whereas in the more recent order they produce
ascorbic acid both in their kidneys and livers (e.g., of the
perching and song birds). Mammals produce ascorbic acid in
the liver. Of the mammals that do not produce ascorbic acid
(e.g., primates and guinea pigs), so-called pseudogenes for
L-gulonolactone oxidase exist. The 164-nucleotide sequence
of exon X of this gene contains nucleotide substitutions
throughout its sequence with a single nucleotide deletion, a
typical example of a pseudogene.
b . Chemistry
Ascorbic acid is of general importance as an antioxidant,
because of its high reducing potential. However, under
some conditions ascorbic acid can also act as a prooxidant.
Ascorbic acid is a 2,3-enediol-L-gulonic acid. Both of
the hydrogens of the enediol group can dissociate, which
Glucose
Galactose
D-Glucuronic Acid
HOCH 2
O
6
HOCH 2 5
HOCH 2
CH
L-Gulonic Acid
HO
L-Gulonolactone Oxidase
CH
O
CH
HO
HO 4
H
OH
H
OH
L-2-Oxogulono-γ-Lactone
Spontaneous
H
O
OH
O
L-Gulono-γ-Lactone
3
O
2
1
OH
OH
Ascorbic Acid
O
O
PAPS
SAM
L-Ascorbic Acid-2-Sulfate
Oxalic Acid + C 4 fragments
or
CO 2 + C 5 and C 4 fragments
2-O-Methyl-L-Ascorbic Acid
FIGURE 23-13 Ascorbic acid synthesis. The direct oxidative pathway for glucose is utilized in those animals that make ascorbic acid. Major metabolites
are the 2-sulfate and 2-methyl derivatives of ascorbic acid, which require phosphoadenosyl phosphosulfate (PAPS) and S-adenosyl methionine
(SAM) as sulfate and methyl donors, respectively. When ascorbate is in excess, catabolic enzymes can effectively decarboxylase or cleave ascorbic acid
(between C-2 and C-3).