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

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Chapter | 23 Vitamins
b . Functions
Enzymes containing flavins are distinguished, because they
are capable of transferring hydrogen directly to molecular
oxygen with the formation of hydrogen peroxide as a product
( Powers, 2003 ; Rivlin, 2007 ). Oxygen prefers to participate
in reactions involving one electron, one hydrogen transfers
proceeding in a stepwise manner. The chemical characteristics
of riboflavin are ideally suited for such reactions. Thus,
with the addition of riboflavin containing cofactors to biological
systems, it is possible for the system to carry out a
range of redox reactions utilizing mechanisms that involve
ion hydride transfers (via NAD or NADP), radical hydrogen
ion transfers (via FMN, FAD) or ascorbic acid, and one electron
plus one proton transfer (via FMN or FAD).
c . Metabolism and Requirements
FMN and FAD in foods are hydrolyzed in the upper gut to
free riboflavin. Riboflavin is absorbed by active processes
and is transported in blood to target tissues in association
with albumin ( Said, 2004 ). Once in cells, riboflavin is
phosphorylated to FMN. FMN is also released from cells
and may bind to albumin for reutilization by other cells.
Active transfer mechanisms are responsible for the uptake
of FMN. In this regard certain drugs (e.g., penicillin and
theophylline) can displace riboflavin from binding proteins
that are important to its transport. Urine is the major route
of excretion for riboflavin, although some FAD is excreted
in bile ( Rivlin, 2007 ).
Requirements for riboflavin are lower than those for
niacin or ascorbic acid. This is primarily because riboflavin
is tightly associated with the oxidases and dehydrogenases
it serves as cofactor; thus, riboflavin turnover is dependent
on the turnover of the proteins to which it is associated.
In some cases, FMN is even covalently bound (e.g.,
as in succinic dehydrogenase). Because of the high affinity
with the enzymes that it serves as a cofactor, in most
animals the half-life of riboflavin is several weeks. Two to
six milligrams of riboflavin per kilogram of diet is required
( Committee on Animal Nutrition, 2001a, 2001b ; Rivlin,
2007 ; Subcommittee on Laboratory Animal Nutrition,
Board on Agriculture, National Research Council, 1995).
When signs of riboflavin deficiency are observed they
usually include lesions of the oral cavity, around the periphery
of the lips, and particularly the angle of the mouth
(cheilosis). There can also be inflammation of the tongue
(glossitis) and accompanying seborrheic dermatitis. In severe
cases of riboflavin deficiency, the filiform papillae of the
tongue are lost and the tongue changes color from its usual
pink to magenta. Anemia and increased vascularization of
the eye are other common signs of riboflavin deficiency in
some animals. Ariboflavinosis is the clinical name for riboflavin
deficiency. Riboflavin deficiency is rarely found in
isolation; it occurs frequently in combination with deficiencies
of other water-soluble vitamins. In addition to anemia,
severe riboflavin deficiency may result in decreased conversion
of vitamin B 6 to its coenzyme form and decreased conversion
of tryptophan to niacin.
Lean meats, eggs, legumes, nuts, green leafy vegetables,
dairy products, and milk provide riboflavin in the
diet. Because riboflavin is destroyed by exposure to light,
foods with riboflavin should not be stored in glass containers
that are exposed to light. Moreover, as grains are a poor
source of riboflavin, deficiencies frequently occur in animals
given diets based on cereal grains. One of the more
striking and specific signs of riboflavin deficiency in birds
is “ curled toe syndrome. ” Curled toe paralysis has been of
economic significance to the broiler industry. In young animals,
growth failure, lost of feathers, or alopecia may be
observed ( Rivlin, 2007 ).
d . Determination of Riboflavin Status
The erythrocyte glutathione reductase activity coefficient
(EGRAC) is the preferred clinical test of riboflavin adequacy.
This enzyme stimulation test measures the reduction
of oxidized glutathione by the enzyme glutathione reductase
with and without the addition of exogenous FAD. In dogs, a
ratio of greater than 1.3 has been taken as deficient. Similar
to the other B-vitamins, analytical approaches involve
hydrophilic interaction chromatography or capillary electrophoresis
using UV, florescence, or mass spectrophotometry
for detection ( Rivlin, 2007 ).
B . Vitamins Directed at Specific Features of
Carbohydrate, Protein, or Lipid Metabolism:
Thiamin, Pyridoxine, and Pantothenic Acid
1 . Thiamin
a . Introduction
Studies related to thiamin were important to the development
of early concepts associated with the role and importance of
vitamins. Another aspect of this work, particularly efforts by
the Dutch medical officer Christian Eijkman, was that the
polyneuritis associated with human beriberi could also be
produced in an experiment animal model by dietary manipulation.
Eijkman and his colleagues fed a diet of polished rice,
presumably low in thiamin, to chickens and observed a characteristic
feature—head retraction. The focus on rice and
the observation that there appeared to be a curative principle
in rice bran led to the eventual isolation of thiamin. This
sequence of discovery provided the underpinnings that led to
the discovery of vitamins as precursors to cofactors and their
roles as regulators ( Goldblith and Joslyn, 1964 ).
b . General Functions
Thiamin is found in cells either as the pyrophosphate (TPP)
or the triphosphate (TPPP) ( Fig. 23-17 ). TPPP predominates
in neural tissue and in the brain ( Davis, 1983 ). There