Deficiencies, nutritional pantothenic acid

D-Pantolactone (Figure 6.3.1) is an important intermediate in the production of d-pantothenic acid, also called vitamin B5. Deficiency of pantothenic acid can result in symptoms such as pathological changes of the skin and mucosa, disorders in the gastrointestinal tract and nervous system, organ changes, and hormonal disorders. Pantothenic acid is used mainly in feed for chicken and pigs and also as a vitamin supply in human nutrition. Its commercial form, the calcium salt, is produced worldwide on a multi-thousand ton scale. 

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). 

It is true that when the selenium and/or methionine in the diet is suboptimum, there is a marked increase in the requirement for vitamin E. However, many stresses and other nutritional deficiencies are also known to increase the tocopherol requirement. For example, carbon tetrachloride toxicity, protein, B12 and folic acid deficiencies (Hove and Hardin, 1951a,b), and Be deficiency (Day and Dinning, 1956), all increase the requirement for a-tocopherol. As for the relationship of ubiquinone to tocopherol, here also, one wonders whether the decreased amount of ubiquinone found in vitamin E deficiency is specific or an incidental effect of one form of inanition, since a deficiency of pantothenic acid, and possibly other deficiencies that affect liver function, will produce similar decreases in ubiquinone. 

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. 

As a result of the reduced activity of the mutase in vitamin B12 deficiency, there is an accumulation of methyhnalonyl CoA, some of which is hydrolyzed to yield methylmalonic acid, which is excreted in the urine. As discussed in Section 10.10.3, this can be exploited as a means of assessing vitamin B12 nutritional status. There may also be some general metabolic acidosis, which has been attributed to depletion of CoA because of the accumulation of methyl-malonyl CoA. However, vitamin B12 deficiency seems to result in increased synthesis of CoA to maintain normal pools of metabolically useable coenzyme. Unlike coenzyme A and acetyl CoA, neither methylmalonyl CoA nor propionyl CoA (which also accumulates in vitamin B12 deficiency) inhibits pantothenate kinase (Section 12.2.1). Thus, as CoA is sequestered in these metabolic intermediates, there is relief of feedback inhibition of its de novo synthesis. At the same time, CoA may be spared by the formation of short-chain fatty acyl carnitine derivatives (Section 14.1.1), which are excreted in increased amounts in vitamin B12 deficiency. In vitamin Bi2-deficient rats, the urinary excretion of acyl carnitine increases from 10 to 11 nmol per day to 120nmolper day (Brass etal., 1990). 

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]

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. 

B12. Barboriak, J. J., and Krehl, W., Effect of ascorbic acid in pantothenic acid deficiency, J. Nutrition 63, 601-609 (1957). 

In the investigation of vitamin deficiencies, it is well to bear in mind that diets deficient in a rangle vitamin produce metabolic disorders which alter the animal s requirement for other nutritional factors. Where pantothenic acid deficiency is concerned, there is evidence that the metabolism of ascorbic acid, biotin, protein, carbohydrate, and fat are involved. 

Other fractions of the vitamin B complex have also been tested for their effect on the survival of young adrenalectomized rats, and it was found that biotin was as effective as pantothenate (Ralli and Dumm, 1952). This is interesting in view of the previous discussion of the interrelation of biotin and pantothenic acid (see Section V.b). In this same series of experiments it was observed that large doses of pyridoxine were toxic to adrenalectomized rats when given after a period of pantothenate deficiency. Thiamine and riboflavin had no influence on survival, but folic acid and vitamin Bu resulted in a moderate improvement. These observations emphasize the interaction of vitamins under various nutritional situations in relation to hormone action. 

The requirement of pyridoxal phosphate for heme synthesis was first shown by a nutritional experiment. In 1950 Wintrobe [47] found that pigs deficient in vitamin Bg formed small, pale, red cells very low in free protoporphyrin, stored excessive iron, and had a h3q)erplastic bone marrow. Lascelles [8] showed that both vitamin Bg and pantothenic acid were required for porphyrin synthesis in Tetrahymena vorax. Similarly, studies by Schulman and Richert [48] showed that heme synthesis in deficient ducklings required vitamin Bg and CoA. 

In medical circles the importance of pantothenic acid as a nutrient is often disregarded because of this universal-occurrence idea and also because it is difficult to produce inhumansaspecificdiseasecondition whichmay be attributed specifically to its deficiency. It would appear that pantothenic acid deficiency (since it is the only organic part of coenzyme A needed nutritionally by mammals) might well cause diffuse adverse effects comparable to those which might be expected to occur in non-osseous tissues as a result of phosphate deficiency. 

The most reasonable interpretation of the extremely diverse effects resulting from pantothenic acid deficiency in various animals (and humans) is based upon the supposition that each tissue in the body is capable of being nourished at various levels of efficiency, and that pantothenic deficiency which can potentially cause damage in every tissue, strikes sometimes here and sometimes there, depending upon many factors which reside in the species or in the afflicted individual animal. Despite the absence of any well-defined human deficiency syndrome there can be no intelligent question regarding the importance of pantothenic acid in human nutrition. 

However, nitrogen is not the only nutritional factor that influences H2S evolution in grape musts as evidenced by Sea et al. (1998) who reported poor correlations between H2S and must nitrogen concentrations. Metabolic depletion of OAS and OAH could be the result of a lack of pantothenic acid, a vitamin required for the synthesis of coenzyme A (GoA), which is necessary for formation of these precursors (Fig. 1.12). In agreement, pantothenic acid deficiency is known to increase H2S pro-... 

Although pantothenic acid and coenzyme A are undoubtedly important in nutrition in man as well as in animals, no evidence of human pantothenic acid deficiency has been recorded. The wide distribution of pantothenic acid in food may explain this failure to observe deficiency even on restricted diets. The human requirement is unknown but probably is not above 5 mg. dailyIn dogs, the need is similar to that for thiamine and ribofiavin. 

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