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

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Chapter | 23 Vitamins
V . VITAMIN-LIKE COMPOUNDS
A . Lipotropic Factors
Nutritional requirements exist for a number of compounds
at specific periods in development, particularly neonatal
development, and periods of rapid growth. These compounds
typically perform specialized transport functions
particularly in relation to fatty acids. Apart from specific
amino acids such as methionine and glycine in feathered
animals, examples include choline, inositol, and carnitine.
1 . Choline
Choline is particularly noteworthy because it plays a key
role in methyl group metabolism, carcinogenesis, and
lipid transport as a component of lecithin ( Garrow, 2007 ).
Choline is normally produced in sufficient amounts; however,
in young growing animals, a positive growth response
can occur upon addition of choline, commercially available
as trimethyl hydroxyethyl ammonium chloride or as
the bitartrate. Choline is generally added to diets to reduce
the need for activated methyl groups supplied by methionine.
It is more economical to add choline for these methyl
groups than to add methionine.
Choline is one of the precursors of acetylcholine.
Choline is also a component of sphingomyelin and lecithin.
Formation of betaine from choline provides important
sources of labile methyl groups for transmethylation reactions.
Choline can also be synthesized de novo from ethanolamine,
when methionine or dimethylcysteine, or betaine is
in adequate supply. The most abundant source of choline in
the diet is lecithin. The primary sign of choline deficiency is
fatty liver. In monkeys, dogs, cats, and rats, it has also been
shown that prolonged choline deficiency results in cirrhosis.
In mice and rats, prolonged deficiency ultimately results in
hepatocellular cancer, a unique example of nutrition deficiency
resulting in neoplasm. Five hundred to 1000 mg of
choline are often added per kilogram of diet ( Garrow, 2007 ).
2 . Inositol
Inositol is also a component of phospholipids and, similar
to choline, results in a fatty liver, if insufficient in supply
( Holub, 1986, 1992 ). Inositol is synthesized from glucose-
6-phosphate after cyclization. In some animals, particularly
gerbils and hamsters, there is a nutritional need for
inositol when they are given diets containing coconut oil.
Myoinositol is plentiful in foodstuffs. The estimated daily
intake for large animals can be as high as 1 or 2g per day.
Inositol is particularly important in cellular signal transduction
and phospholipid assembly. Plasma levels of inositol are
increased during renal disease and nephrectomy. The presence
of myoinositol hexabisphosphate (InsP6) in biological
fluids (blood, urine, saliva, interstitial fluid) of animals has
been clearly demonstrated. The existence of intracellular
InsP6 in mammalian cells has also been established. A
relationship between InsP6 ingestion and the InsP6 distribution
in various tissues exists. Whereas intracellular inositol
depends on endogenous synthesis, depletion of extracellular
InsP6 occurs at high rates when InsP6-poor diets are consumed.
Consequently, there are probably health benefits that
are linked to dietary inositol and InsP6 intake. The suggestion
that inositol is important in young animals came from
studies carried out throughout the 1970s and 1980s. In particular,
it was noted that female gerbils fed a diet containing
high coconut oil (relatively saturated) develop an intestinal
lipodystrophy that is not seen in animals fed a diet containing
20% safflower oil (relatively unsaturated) or a diet of
20% coconut oil supplemented with 0.1% inositol. The level
of inositol in the intestinal tissue of animals fed the coconut
oil diet not supplemented with inositol has been shown to
decrease. Clearance of lipid (i.e., resolution of the lipodystrophy)
was dependent on inositol ( Holub, 1986, 1992 ).
3 . Carnitine
Oxidation of fatty acids requires their transportation from the
cytosol into the mitochondrial matrix where they undergo
β -oxidation. Carnitine plays a major role in this transport
process by accepting activated fatty acids at the outer
mitochondrial membrane. Carnitine comes both from the
diet and synthesis from lysine by a process that is ascorbic
acid dependent. These steps are not carried out efficiently
in some newborns. Given the importance of carnitine to
β -oxidation of long-chain fatty acids, carnitine deficiency
can have profound effects on lipid utilization. An inherited
carnitine deficiency has been recognized in some dogs such
as the boxer ( Keene, 1991 ; Keene et al., 1991 ; Kittleson
et al., 1997 ; Mc Entee et al., 2001 ). Moreover, American
cocker spaniels that are taurine deficient have been shown
to be responsive to a combination of taurine and carnitine
supplementation ( Kittleson et al., 1997 ).
Meats and dairy products in contrast to plant foods are
good sources of carnitine. Cereal grains besides being low
in carnitine are also generally low in the precursors of carnitine:
lysine and methionine. Drugs, such as mildronate
(3-(2, 2, 2,-trimethylhydrazinium) propionate) can also lower
carnitine levels and inhibit synthesis. Mildronate is a
butyrobetaine analogue that is known to inhibit gammabutyrobetaine
hydroxylase, the enzyme catalyzing the
last step of carnitine biosynthesis. In humans, mildronate
is used to ameliorate cardiac function during ischemia by
modulating myocardial fatty acid oxidation to the more
favorable glucose oxidation. When given to pregnant animals,
carnitine levels increase in the milk. Correspondingly,
an increase in triglyceride levels is observed in liver, heart,
and muscle of mildronate pups (i.e., biochemical modifications
compatible with a carnitine deficiency status).