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OCR for page 67
Pantothenic Acic!
Williams (1939) first isolated pantothenic acid as a
growth factor for yeast. The vitamin was also investi-
gated as a growth-promoting factor for lactic acid bacte-
ria. Pantothenic acid is widely distributed in biological
materials. Subsequent to its isolation as a microbial
growth factor, it was shown that pantothenic acid is
identical to an antidermatitis factor for chicks and a
growth-promoting factor for rats (Fox, 1984; Olson,
1984~. The presence of pantothenic acid as a component
of coenzyme A (L`ipmann et al., 1947) indicated the vita-
min's biochemical role and led to the demonstration that
pantothenic acid-deficient rats had defects in the ability
to metabolize fatty acids.
NUTRITIONAL ROLE
Dietary Requirements of Various Species
Signs of pantothenic acid deficiency vary in different
species (Sauberlich, 1980; Fox, 1984~. An effect on
growth response usually can be demonstrated. Most
pantothenic acid-deficient laboratory animals exhibit
dermatitis, achromotrichia, and nasal porphyrin excre-
tion. Pantothenic acid-deficient poultry exhibit a feath-
ering disorder, fatty livers, and a characteristic
dermatitis in the corners of the mouth.
Deficiency signs are readily produced in most labora-
tory animals. The dietary requirements for rats, mice,
and guinea pigs are 8 to 20 mg/kg of diet; for chicks, 10
mg/kg; for swine, 13 mg/kg; and for dogs and cats, 10
mg/kg. No daily dietary requirements for pantothenic
acid have been established for ruminants, horses, or
humans. Estimates of human adult daily intakes of the
vitamin in the United States range from 5 to 20 mg/day
(Sauberlich, 1980~.
67
Biochemical Functions
Pantothenic acid is a component of coenzyme A, acyl
CoA synthetase, and acyl carrier protein. The coen-
zyme form of the vitamin is therefore responsible for
acyl group transfer reactions. The acyl derivatives of
coenzyme A are activated thiol esters of the h-mercapto-
ethylamine portion of the molecule, which is attached to
the carboxyl group of pantothenic acid to form the ac-
tive coenzyme. These activated acyl groups are in-
volved in condensations, acyl group exchanges, and
acyl group transfers catalyzed by a number of enzymes.
Coenzyme A derivatives are also involved in fatty acid
degradation, and fatty acids are synthesized as acyl car-
rier protein derivatives.
FORMS OF THE VITAMIN
Pantothenic acid consists of pantoic acid ((x,~-dihy-
droxy-$,h'-dimethylbutyric acid) joined to ,B-alanine by
an amide bond (Figure 15~. Much of the pantothenic acid
in tissues consists of the coenzyme forms of the vitamin.
These forms all have ,B-mercaptoethylamine bound as
an amide to pantothenic acid and have a 4'-phosphate
joined to a 3',5'-adenosine diphosphate (ADP) by a pyro-
phosphate in coenzyme A, or to a serine residue of acyl
carrier protein or acyl CoA synthetase. This mixture of
coenzymes is to a large extent acylated in tissues. Anal-
yses of the vitamin in foods and tissues have most often
been carried out by microbiological methods, and enzy-
matic digestion has been used to liberate pantothenic
acid from the various coenzyme forms. The form used in
the supplementation of animal feeds is the salt, calcium
pantothenate.
OCR for page 68
6~3 Vitamin Tolerance of Animals
ABSORPTION AND METABOLISM
CH3 OH O
1 1 11
HO CH2 ---- C CH C N CH2 CH2 COOH
1 1
CH3 H
Pantothenic acid
SH
H2
~H2
NH
C-O
H2
~H2
NH
C=0
CHOH
CH3-C CH3
l H2
o
-O-P=0
o
I NH2
-o P-0 1
O ~C ~ ON
I HC Il I
CH \N,C ~ ITCH
HUH
O OH
PO3
Coenzyme A
FIGURE 15
coenzyme A.
,B- Mercaptoethylamine
Pantothenic acid
1
-
Adenine
Ribose 3 -phosphate
Chemical structures of pantothenic acid and
Pantothenic acid activity is widely distributed in feeds
and foods, where it is present as a mixture of coenzyme
forms. These forms of the vitamin are presumably hy-
drolyzed in the intestine. Serum contains predomi-
nantly free pantothenic acid. Cellular enzymes convert
pantothenic acid to coenzyme A through a pathway that
involves phosphorylation, addition of the h-mercapto-
ethylamine group, and, finally, addition of the nucleo-
tide. Excess pantothenic acid is excreted in the urine,
and changes in dietary intake can be followed by urinary
excretion (Fox, 19841.
HYPERVITAMINOSIS
Pantothenic acid is generally regarded as nontoxic
(Omaye, 1984~. No adverse reactions have been re-
ported in any species following the ingestion of elevated
levels of pantothenic acid in the diet. Unna and Greslin
(1941) determined an acute LD50 value for calcium pan-
tothenate of about 1 g/kg of BW by parenteral injection
for the rat but no toxicity at a dose of 10 g/kg of BW
administered orally. They also reported that rats fed 200
mg of calcium pantothenate/day (about 20 g/kg of diet)
for 190 days showed no adverse effects as far as growth
nor any evidence of gross pathology. Wirtschafter and
Walsh (1962) reported liver damage, as measured by
lipid deposition and elevated serum glutamic/
oxaloacetate transaminase activities, following the in-
tramuscular injection of 20 mg of sodium pantothenate
(about 80 mg/kg of BW) to rats. The severity of the
response increased when greater doses were adminis-
tered.
PRESUMED UPPER SAFE LEVELS
No adverse responses to the ingestion of pantothenic
acid have been documented. The upper limits of pre-
sumed safe dietary levels cannot be established. It is
clear, however, that dietary levels of at least 20 g of
pantothenic acid/kg can be tolerated by most species.
SUMMARY
1. Pantothenic acid can be administered orally or in
the diet at an intake of 10 g/kg of BW with no adverse
effects.
2. Parenterally administered pantothenic acid has an
acute LD50 of about 1 g/kg of BW for the rat. Doses of
about 80 mg/kg of BW have been shown to be associated
OCR for page 69
Pantothenic Acic! 69
with nonfatal liver damage. This amount is approxi-
mately 100 times the daily dietary requirement for the
vitamin.
REFERENCES
Fox, H. M. 1984. Pantothenic acid. Pp. 437-458 in Handbook of
Vitamins, L. J. Machlin, ed. New York: Marcel Dekker.
Lipmann, F., N. O. Kaplan, G. D. Novelli, L. C. Tuttle, and B. M.
Guirard.1947. Coenzyme for acetylation, a pantothenic acid deriva-
tive. J. Biol. Chem. 167:869.
Olson, R. E. 1984. Pantothenic acid. Pp. 377-382 in Present Knowl-
edge in Nutrition, R. E. Olson, ed. Washington, D.C.: The Nutrition
Foundation.
Omaye, S. T. 1984. Safety of megavitamin therapy. Adv. Exp. Med.
Biol. 177:169.
Sauberlich, H. E. 1980. Pantothenic acid. Pp. 209-215 in Modern
Nutrition in Health and Disease, R. S. Goodhart and M. E. Shils,
eds. Philadelphia: Lea & Febiger.
Unna, K., and J. S. Greslin.1941. Studies of the toxicity and pharma-
cology of pantothenic acid. J. Pharmacol. Exp. Ther. 73:85.
Williams, R. J.1939. Pantothenic acid-A vitamin. Science 89:486.
Wirtschafter, Z. T., and J. R. Walsh. 1962. Hepatocellular lipid
changes produced by pantothenic acid excess. Ann. Surg. 15:976.
Representative terms from entire chapter:
coenzyme forms
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