Pantothenic Acid Deficiency in Man1

Hodges, Robert E.; Ohlson, Margaret A.; Bean, William B.

doi:10.1172/jci103756

Cited by 77 publications

(27 citation statements)

References 29 publications

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“…The synthesis of essential fats, cholesterol, and steroid hormones requires CoA, as does the synthesis of the neurotransmitter, acetylcholine, and the hormone, melatonin (2). Metabolism of a number of drugs and toxins by the liver requires CoA (34). Most acetylated proteins in the body have been modified by the addition of an acetate group that was donated by CoA.…”

Section: Discussionmentioning

confidence: 99%

Effects of Excess Pantothenic Acid Administration on the Other Water-Soluble Vitamin Metabolisms in Rats

Shibata

Takahashi

Fukuwatari

et al. 2005

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryTo acquire the data concerning the tolerable upper intake level which prevents health problems from an excessive intake of pantothenic acid, an animal experiment was done. Rats of the Wistar strain (male, 3wk old) were fed on a diet which contains 0%, 0.0016% (control group), 1%, or 3% calcium pantothenate for 29d. The amount of weight increase, the food intake, and the organ weights were measured, as well as the pantothenic acid contents in urine, the liver and blood. Moreover, to learn the influence of excessive pan tothenic acid on other water-soluble vitamin metabolism, thiamin, riboflavin, a vitamin B6 catabolite, the niacin catabolites, and ascorbic acid in urine were measured. As for the 3% addition group, enlargement of the testis, diarrhea, and hair damage were observed, and the amount of weight increase and the food intake were less than those of the control group. However, abnormality was not seen in the 1% addition group. The amount of pantothenic acid in urine, the liver, and blood showed a high correlation with intake level of pantothenic acid. It was only for 4-pyridoxic acid, a vitamin B6 catabolite, in urine that a remarkable dif ference was observed against the control group. Moreover, the (2-Py+4-Py)/MNA excretion ratio for these metabolites of the nicotinamide also indicated a low value in the 3% pan tothenic acid group. As for the calcium pantothenate, it was found that the 3% level in the diet was the lowest-observed-adverse-effect-level (LOAEL) and the 1% level was the no observed-adverse-effect-level (NOAEL).

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Section: Discussionmentioning

confidence: 99%

Effects of Excess Pantothenic Acid Administration on the Other Water-Soluble Vitamin Metabolisms in Rats

Shibata

Takahashi

Fukuwatari

et al. 2005

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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“…Cysteamine has numerous pharmacologic actions (21) and hormonal effects (47,48). Pantothenate deficiency has been reported to lower blood cholesterol levels in the rat (49) and dog (50), but this was not demonstrated in humans (51). We know ofno reports investigating hypolipemic properties of cysteamine or pantothenate.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of pantethine in cystinosis.

et al. 1985

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D-Pantethine is a conjugate of the vitamin pantothenic acid and the low-molecular-weight aminothiol cysteamine. Pantethine is an experimental hypolipemic agent and has been suggested as a source of cysteamine in the treatment of nephropathic cystinosis. We treated four cystinotic children with 70-1,000 mg/kg per d oral D-pantethine and studied its metabolism. Pantethine was rapidly hydrolyzed to pantothenic acid and cysteamine; we could not detect pantethine in plasma after oral administration. The responsible enzyme, "pantetheinase," was highly active in homogenates of small intestinal mucosa and plasma. The Michaelis constant of the rat intestinal enzyme was 4.6 MM and its pH profile showed a broad plateau between 4 and 9. Pantothenate pharmacokinetics after orally administered pantethine followed an open two-compartment model with slow vitamin elimination (t1/2 = 28 h). Peak plasma pantothenate occurred at 2.5 h and levels over 250 MM were seen at 300 times normal. Apparent total body storage of pantothenate was significant (25 mg/kg), and plasma levels were elevated threefold for months after pantethine therapy. Plasma cysteamine concentrations after pantethine were similar to those reported after equivalent doses of cysteamine. However, at best only 80% white blood cell cystine depletion occurred. We conclude that pantethine is probably less effective than cysteamine in the treatment of nephropathic cystinosis and should only be considered in cases of cysteamine intolerance. Serum cholesterol was decreased an average of 14%, which supports the potential clinical significance of pantethine as a hypolipemic agent. Rapid in vivo hydrolysis of pantethine suggests that pantothenate or cysteamine may be the effectors of its hypolipemic action.

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“…6, No. 1,1989 experimental period than did the ad libitum fed controls. The mean food consumption of AL rats was 16.7 g/day, whereas PAD and Pw rats ingested only 12.2 and 9.2 g food/day, respectively.…”

Section: Resultsmentioning

confidence: 85%

“…6, No. 1,1989 T. REMER and K. PIETRZIK lower corticosterone secretion ascertained by Goodman [13] for PA-deficient compared with restrictedly fed control rats in a study without ACTH administration. Owing to the biphasic pattern of plasma corticosterone (second rise in the evening) seen in Pw animals, the adrenocortical stress activity of this control group varies from the stress situation discernible in PA-deficient animals.…”

Section: Discussionmentioning

confidence: 94%

“…Because of the widespread occurrence of pantothenic acid (PA) in foods , deficiency symptoms in humans have not been observed except in cases of severe malnutrition [ 1 ] and in volunteers fed either the antagonist f2-methylpanthothenic acid or a semisynthetic diet virtually free of pantothenate [2,3]. Thus many of the known symptoms of a manifest PA deficiency have been seen only in experimental animals, which can be more rigorously controlled.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Pantothenate Deficiency on Steroid Hormone Secretion in Rats

Pietrzik

1989

J. Clin. Biochem. Nutr.

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SummaryThe effect of pantothenic acid (PA) deficiency on the adrenocortical function was investigated in young male rats fed a PAdeficient (PAD) diet over a period of about three months. Pair-weight (PW) and ad libitum (AL) fed rats served as controls. Basal 08.00 h (lights on) plasma levels of corticosterone were regularly found to be reduced in PAD and AL rats compared with those in PW animals. Investigation of the circadian rhythm of plasma corticosterone revealed that the elevated 08.00 h hormone concentrations of PW rats are due to a biphasic 24-h pattern of plasma corticosterone with a distinct glucocorticoid peak at lights on and another one at lights off (20.00 h), whereas PAD and AL rats only show one clear increase in plasma corticosterone levels at the beginning of the dark period. However, the evening glucocorticoid peak of the PAD rats was markedly higher than that of the PW and AL groups. Thus an adrenocortical overactivity is ascertained in PA deficiency which is presumably responsible for the adrenal hypertrophy generally observed in earlier studies on PA depletion in rats. Multiple examinations of the secretory capacity for corticosterone, each carried out half an hour after i.m. administration of 2.5 IU ACTH1-24, revealed comparable plasma responses to supraphysiological ACTH stimulation in PAD, PW, and AL rats. Therefore we concluded that corticosterone secretion is not impaired in PA deficiency, at least not that elicited for short periods by adrenocortical overstimulation. Additional measurem ents of the adrenal cholesterol content and the circadian plasma levels of dehydroepiandrosterone-sulphate were carried out in all three diet groups. The respective results are discussed with regard to the stress situation produced by the experimental PA deficiency.

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Pantothenic Acid Deficiency in Man1

Cited by 77 publications

References 29 publications

Effects of Excess Pantothenic Acid Administration on the Other Water-Soluble Vitamin Metabolisms in Rats

Effects of Excess Pantothenic Acid Administration on the Other Water-Soluble Vitamin Metabolisms in Rats

Metabolism of pantethine in cystinosis.

Effects of Pantothenate Deficiency on Steroid Hormone Secretion in Rats

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