Pantothenic deficiency

Pantothenate deficiency is rare, occurring only in cases of severe malnutrition characteristic symptoms include vomiting, intestinal distress, insomnia, fatigue and occasional diarrhoea. Pantothenate is widespread in foods meat, fish, poulty, whole-grain cereals and legumes are particularly good sources. Although no RDA or RNI value has been established for panthothenate, safe and adequate intake of this vitamin for adults is estimated to be 3-7 mg day-1. Pantothenate is non-toxic at doses up to 10 g day-1. 

The unusual course of amino acid accumulation in biotin- and pantothenate-deficient cells (Figure 3) also has been found to be markedly influenced by sucrose and other osmotic protectants, as well as by acetate. The course of glutamic acid uptake by biotin-deficient cells in the... 

With biotin-deficient cells low concentrations of acetate will substitute for high concentrations of sucrose in restoring uptake to normal levels (22). Biotin stimulates slightly when provided in addition to acetate. Pantothenate-deficient cells respond dramatically to acetate only in the presence of this vitamin. This behavior probably reflects the involvement of coenzyme A in the process which restores a normal accumulation pattern. 

Therefore, the three vitamin deficiencies so far studied in detail appear to affect amino acid transport and accumulation in similar but indirect ways. The accumulation defect is most pronounced in vitamin B6-deficient cells, for which there is also strong evidence implicating an abnormality in cell wall composition as a likely source of the change in transport activity. Direct evidence for a cell wall change in biotin- and pantothenate-deficient cells has not yet been obtained. The possibility remains, therefore, that the change in accumulation activity may be caused by an abnormality in some other structural component such as the peripheral cell membrane. 

There are no functional tests of pantothenic acid nutritional status that are generally applicable. Deficiency of pantothenic acid impairs the ability to acetylate a variety of drugs, such as p-aminobenzoic acid, but this has not been developed as an index of vitamin status. The capacity to acetylate drugs is genetically determined neither experimental pantothenate deficiency nor the administration of supplements affects the determination of fast or slow acetylator status (Pietrzik et al., 1975 Vas et al., 1990). 

Wittwer CT, Beck S, Peterson M, Davidson R, Wilson DE, and Hansen RG (1990) Mild pantothenate deficiency in rats elevates serum triglyceride and free fatty acid levels. Journal of Nutrition 120,719-25. 

Symptoms of pantothenate deficiency are difficult to assess since they are subtle and resemble those of other B vitamin deficiencies. 

Smith, C. M., Narrow, C. M., Kendrick, Z. V, and Steffan, C. (1987). The effect of pantothenate deficiency in mice on their metabolic response to fast and exercise. Alc/fflwfKrn 36, 115-121. 

CoASH is synthesized from the vitamin pantothenate in a sequence of reactions which phos-phorylate pantothenate, add the sulfhydryl portion of CoA from cysteine, and then add AMP and an additional phosphate group from ATP (see Fig. 8.12). Pantothenate is widely distributed in foods (pantos means everywhere), so it is unlikely that Ann O Rexia has developed a pantothenate deficiency. Although CoA is required in approximately 100 different reactions in mammalian cells, no Recommended Daily Allowance (RDA) has been established for pantothenate, in part because indicators have not yet been found which specifically and sensitively reflect a deficiency of this vitamin in the human. The reported symptoms of pantothenate deficiency (fatigue, nausea, and loss of appetite) are characteristic of vitamin deficiencies in general. 

Both pantothenate deficiency and high pantothenate diets in experimental animals are associated with changes in the physiological and biochemical responses to various forms of stress. A limited amount of... 

In pantothenate-deficient intact rats subjected to forced swimming or injected with ACTH, the typical lymphocytic response was abolished (Dumm et al., 1949). If the deficient animals received a high pantothenic acid diet for 4 days, a more nearly normal response followed either swimming or the injection of ACTH. These findings were attributed to the effects of pantothenic acid deficiency on the structure and function of the adrenal cortex. Winters el al. (1952a) observed that the lymphopenic and eosinopenic responses to ACTH and epinephrine were abolished following a 5- to 6-week period of pantothenate deficiency. However, fol-... 

Experiments of this type are subject to several intrinsic difficulties which Winters discusses in some detail. Adrenal function can be assayed by physiological responses of this type only if the tissue on which the adrenal hormone acts is functioning normally. Owing to the critical role of coenzyme A in intermediary metabolism, the maintenance of normal function in any tissue during severe pantothenate deficiency is doubtful. However, experiments attempting to define adrenocortical function by studies of carbohydrate metabolism in situations of severe pantothenate deficiency are partially justified by the finding of Olson and Kaplan (1948) that in the rat the adrenal cortex suffers an earlier depletion of coenzyme A than does the liver. After 3 weeks of pantothenate deficiency, coenzyme A was significantly decreased in the adrenal and heart, whereas it was still at normal levels in the liver and kidney. After 6 weeks on the... 

In view of the fact that acetylation does not depend upon adrenal function, it seems evident that the disturbance in acetylation occurring in pantothenate deficiency is not due to the associated adrenal changes. 

Further evidence of the interrelation of ascorbic acid and pantothenic acid is the fact that the addition of ascorbic acid (in a concentration of 2 % of the diet) to a pantothenate-deficient diet somewhat protected rats against the symptoms of pantothenate deficiency (Daft, 1951 Daft and Schwarz, 1952). 

Studies on the excretion of 17-ketosteroids by female rats on a diet deficient in pantothenate have not been reported. These data would be interesting because of the observations of Dorfman (1947), who reported a sharp decrease in the excretion of 17-ketosteroids in female monkeys and guinea pigs following adrenalectomy. It was also observed that in the scorbutic female guinea pig (Dorfman, 1947 Banerjee and Deb, 1952) there was a sharp decrease in the excretion of 17-ketosteroids. These observations indicate that the adrenal is the source of these steroids and that diets deficient in ascorbic acid, which affects the adrenals, will also decrease the synthesis of these steroids. In view of the fact that there is a disturbance of ascorbic acid metabolism in pantothenate-deficient rats, it may well be that this would contribute to a disturbance in the synthesis of the 17-ketosteroids in the pantothenate deficiency. 

In view of the role of coenzyme A in the oxidation and transfer of acetyl groups, it is not surprising that pantothenic acid has been implicated in both the oxidation and synthesis of lipids. Butyric and caproic acids were oxidized by liver homogenates from pantothenate-deficient... 

---