Subject pantothenic acid

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

Pantothenic acid is relatively labile (185,186). In the dry form, it is hygroscopic and unstable in solution its stability is strongly pH dependent, being greatest at pH 4-5. It is subject to hydrolytic cleavage to pantoic acid and /3-alaninc in more acidic or alkaline solutions. Pantothenic acid is very soluble in water, alcohols, and dioxane, less soluble in diethyl ether and acetone, and insoluble in benzene and chloroform. 

It should be noted that deficiency states for some vitamins (e.g., pantothenic acid) are practically unknown in human beings. In such cases, deficiency states may be simulated by feeding the subject an appropriate vitamin antagonist. In another series of situations, vitamin deficiencies can be brought about by interfering with their absorption intentionally or may be the result of a disease process. Thus, fat-soluble vitamin deficiency may develop in cases of fat malabsorption syndromes (steatorrhea) sprue, pancreatic insufficiency, and bile duct obstruction. 

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]

Plasma and urinary levels of pantothenic acid have been measured in dietary surveys as well as in controlled studies of the vitamin deficiency. One fairly recent study with human subjects involved the feeding of a pantothenic acid-free diet for 9 weeks. The urinary pantothenic acid levels (4-6 mg/day) in vitamin-sufficient subjects were roughly half that of the intake (10 mg/day). With consumption of the vitamin-free diet, urinary pantothenic acid levels gradually declined to about 0.8 mg/day over the 9-week period (Fry et ai., 1976). Both urinary and blood serum levels of pantothenate have been used to assess dietary status. Values from urinary measurements seem to be somewhat better correlated with intake of this vitamin, than blood measurements data (Berg, 1997). 

Pantothenic acid is taken in as dietary CoA compounds and dCphosphopantetheine and hydrolyzed by pyrophosphatase and phosphatase in the intestinal lumen to dephospho-CoA, phosphopantetheine, and pantetheine. This is further hydrolyzed to pantethenic acid. The vitamin is primarily absorbed as pantothenic acid by a saturable process at low concentrations and by simple diffusion at higher ones. The saturable process is facilitated by a sodium-dependent multivitamin transporter, for which biotin and lipoate compete. After absorption, pantothenic acid enters the circulation and is taken up by cells in a manner similar to its intestinal adsorption. The synthesis of CoA from pantothenate is regulated by pantothenate kinase, which itself is subject to negative feedback from the products CoA and acyi-CoA. The steps involved were outlined above. Pantothenic acid is excreted in the urine after hydrolysis of CoA compounds by enzymes that cleave phosphate and the cys-teamine moieties. Only a small fraction of pantothenate is secreted into milk and even less into colostrum. 

The widespread availability of pantothenic acid in food is commensurate with its many roles and makes an uncomplicated dietary deficiency of pantothenate unlikely in humans. Symptoms have been produced in a few volunteers who have received co-methylpantothenic acid as an antagonist and in people fed semisynthetic diets virtually free of pantothenate. Subjects became irascible and developed postural hypotension and rapid heart rate on exertion, epigastric distress with anorexia and constipation, numbness and tingling of the hands and feet, hyperactive deep tendon... 

Since the original observation of Lipmann et cd. (1947) on the presence of pantothenic acid in coenzyme A, the purification and chemical structure of the coenzyme has been the subject of intensive investigation in many laboratories (Snell et al., 1950 Lynen and Reichert, 1951 Novell et al, 1951 Baddiley and Thain, 1951). As formulated at present, coenzyme A contains 1 adenine, 1 ribose, 1 sulfur, and 3 phosphates per pantothenate. Evidence presented by Lynen and Roichert (1951) indicates that acetyl-CoA, which is now considered synonomous with active acetate, is an acetylated mercaptan. A tentative structure of acetyl-CoA is given below. 

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-... 

Pantothenic acid analyses performed by Ferrari and Allegri (1956) on liver. samples from 10 normal subjects, aged 19 to 64 years, similarly showed... 

Table I summarizes the effects of the various deficiencies of the vitamin B complex upon the response to a variety of antigenic stimuli in different test animals. It is the reviewers opinion that, with the exception of the criticisms already made, this table represents the results of well-controlled, adequate experiments. It is quite apparent that the individual members of the vitamin B complex play a very important role in determining antibody response. Their absence may produce a marked impairment in antibody production. Generalizations on this subject are dangerous, but it would appear that pyridoxine, pantothenic acid, and folic acid deficiencies show the most consistent deleterious effects upon antibody production. It is also apparent that the effects of the individual deficiencies may vary widely depending upon the antigen employed.

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