Pantothenic acid, deficiency

Pathological changes in pantothenic acid-deficient animals have been described in the rat (Sullivan and Nicholls ), the mouse (Jones et and the pig (Wintrobe et aZ. ). 

The skin of the rat, according to Sullivan and Nicholls, showed loss of hair around the ears and the snout, the remainder of the hair, if pigmented, becoming gray. There was hyperkeratosis and increase of the prickle cell layer in the skin (acanthosis). The whole skin eventually became atrophic. 

There was hyperemia of the intestine, particularly in the large intestine. Ulcers developed in the lymphoid follicles of the walls and sometimes led to perforation (Fig. 40). The cells of the epithelium became atrophic, the process starting as small atrophic foci which eventually spread and covered 

This suggested that in pantothenic acid deficiency the adrenal had lost its ability to produce steroids in response to anterior pituitary stimulation. 

Cowgill et stated that their own and previous work had established that a characteristic lesion developed in the adrenal cortex in response to pantothenic acid deficiency and that this lesion was more severe following treatment with ACTH but that cortisone prevented development microscopically. They concluded that the above work together with functional studies on carbohydrate metabolism supported the view that in pantothenic acid deficiency there was inadequate cortical function. They believe that pantothenic acid acting as coenzyme A is necessary for the synthesis of adrenal steroids. 

Acetyl CoA acetyltransferase, a key enzyme of ketogenesis, and 3-oxo-acyl CoA thiolase, involved in -oxidation, bind CoA by formation of a disulfide bond to cysteine, a reaction that can be reversed by glutathione and other sulfhydryl reagents. The physiological significance of this reaction with CoA, which inactivates the enzymes, is not clear (Quandt and Huth, 1984, 1985 Schwerdt and Huth, 1993). 

Pantothenic acid is widely distributed in foods, and because it is absorbed throughout the small intestine, it is likely that intestinal bacterial synthesis also makes a contribution to pantothenic acid nutrition. As a result, deficiency has not been unequivocaUyreportedinhumanbeings except in specific depletion studies, which have also frequently used the antagonist -methyl pantothenic acid. 

Pantothenic acid deficiency in black and brown rats leads to a loss of fur color - at one time, pantothenic acid was known as the antigray hair factor. There is no evidence that the normal graying of hair with age is related to pantothenic acid nutrition, nor that pantothenic acid supplements have any effect on hair color. 

In pantothenic acid-deficient rats, tissue CoA is depleted, affecting mainly the peroxisomal oxidation of fatty acids, which is mainly concerned with detoxication mitochondrial /3 -oxidation, which is an essential energy-yielding pathway, is spared to a great extent (Youssef et al., 1997). However, relatively moderate deficiency in animals results in increased plasma triacylglycerol and nonesterifled fatty acids, suggesting some impairment of lipid metabolism (Wittwer et al., 1990). 

Rats on a pantothenic acid-free diet show rapid depletion of adrenal corticosteroids, and reduced production of the steroids in isolated adrenal glands in response to stimulation with adrenocorticotrophic hormone (ACTH). This presumably reflects the role of acetyl CoA in the synthesis of steroids deficiency also results in atrophy of the seminiferous mbules of male rats and delayed sexual maturation in females. As deficiency progresses, there is enlargement, then congestion, and finally hemorrhage, of the adrenal cortex. In young animals, but not in adults, pantothenic acid deprivation eventually leads to necrosis of the adrenal cortex. 

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The 4-phosphopantetheine group of CoA is also utilized (for essentially the same purposes) in acyl carrier proteins (ACPs) involved in fatty acid biosynthesis (see Chapter 25). In acyl carrier proteins, the 4-phosphopantetheine is covalently linked to a serine hydroxyl group. Pantothenic acid is an essential factor for the metabolism of fat, protein, and carbohydrates in the tricarboxylic acid cycle and other pathways. In view of its universal importance in metabolism, it is surprising that pantothenic acid deficiencies are not a more serious problem in humans, but this vitamin is abundant in almost all foods, so that deficiencies are rarely observed. 

B27. Bean, W. B., and Hodges, R. E., Pantothenic acid deficiency induced in human subjects. Proc. Exptl. Biol. Med. 86, 693-698 (1954). 

Very little is known about the pantothenic acid needs of human beings even though it has been about 14 years since this vitamin in synthetic form became available. The backwardness is due in part to the fact that pantothenic acid deficiency often does not give rise to... 

Many different types of lesions have been observed (very often at autopsy) in animals suffering from severe pantothenic acid deficiency. These may involve the skin, the adrenals, the entire gastrointestinal tract, nerves, and spinal cord. Functionally, in chickens fertility may be reduced by pantothenic acid deficiency to practically zero64 without any outward signs being shown by the fowls. Recently, pantothenic acid deficiency has been found to produce duodenal ulcers in about 60 per cent of the rats tested.65 It is required for bone development66 and is implicated in antibody responses.67... 

Pantothenic acid deficiency manifests itself by symptoms of neuromuscular degeneration and adrenocortical insufficiency. 

The symptoms of pantothenic acid deficiency have not been clinically described. Since pantothenic acid is a ubiquitous vitamin, isolated deficiency is unlikely. However, marginal deficiency may exist in persons with general malnutrition. 

There is no record of pantothenic acid deficiency in humans, since all food contains sufficient quantities of this vitamin. Experimentally, however, neurological, gastrointestinal, and cardiovascular symptoms result from a diet lacking in pantothenic acid. 

Pantothenic acid is a component of coenzyme A, which functions in the transfer of acyl groups (Figure 28.17). Coenzyme A contains a thiol group that carries acyl compounds as activated thiol esters. Examples of such structures are succinyl CoA, fatty acyl CoA, and acetyl CoA. Pantothenic acid is also a component of fatty acid synthase (see p. 182). Eggs, liver, and yeast are the most important sources of pan tothenic acid, although the vitamin is widely distributed. Pantothenic acid deficiency is not well characterized in humans, and no RDA has been established. 

Pantothenic acid deficiency appears only in cases of severe malnutrition, and it is usually characterized by a burning sensation in the feet and lower legs (19,186). 

Vitamin B5 (pantothenic acid) (Figure 2.28) is a very widely distributed water-soluble vitamin, though yeast, liver, and cereals provide rich sources. Even though animals must obtain the vitamin through the diet, pantothenic acid deficiency is rare, since most foods provide... 

It is apparent that at this stage of development definitive conclusions are premature, and that this aspect of amino acid and lipide metabolism will be pursued vigorously in the near future. It is of considerable interest to us that biotin and pantothenic acid deficiencies affect amino acid transport in L. arabinosus, since both vitamins are known to play a prominent role in lipide biosynthesis. We are currently reexamining the turnover of lipide fractions in nutritionally normal and vitamin-deficient cell types to determine whether there is some relation between this aspect of metabolism and amino acid transport. In any case, the nature of the catalytic steps involved in amino acid transport is still unknown to us. They probably occur in the peripheral cell membrane, but even this elementary and widely accepted belief will require additional study before it can be accepted beyond doubt as an established fact. 

Deficiency is well documented in chickens, which develop a pantothenic acid-responsive dermatitis. Other experimental animals show a variety of abnormalities from pantothenic acid deficiency. In human beings dietary deficiency has not been reliably documented, although it has been implicated in the burning foot syndrome (nutritional melalgia). Subjects maintained on pantothenic acid-deficient diets or given the antagonist [Pg.345]

Deficient animals have an impaired ability to respond to metabolic and physical stress as a result of this decreased adrenocortical hormone synthesis, although this may be accompanied by enhanced sensitivity of target tissues to hormone action. Some strains of rat are susceptible to the development of duodenal ulcers in pantothenic acid deficiency. Ulceration can be prevented by adrenalectomy and is exacerbated by administration of glucocorticoid hormones. 

Dogs develop severe and potentially fatal hypoglycemia in pantothenic acid deficiency - this responds to the administration of glucocorticoid hormones, suggesting that it is secondary to impairment of adrenal cortical function. 

Human Pantothenic Acid Deficiency - The Burning Foot Syndrome... 

Urinary excretion of acyl carnitine esters increases considerably in a variety of conditions involving organic aciduria carnitine acts to spare CoA and pantothenic acid (Section 12.2), by releasing the coenzyme from otherwise nonmetabolizable esters that would trap the coenzyme and cause functional pantothenic acid deficiency. 

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