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Pantothenic acid content of human milk.

One-day diets were recorded by 22 lactating women 1 to 6 months postpartum. Pantothenic acid content of the diets was estimated using a published table of pantothenic acid values for food. The mean pantothenic acid intake of the lactating women was 7.6 mg/day over the 6-month period. The day after diet recording, the women collected two samples of breast milk during the first feeding of the day after 5 AM. The first sample was obtained at the beginning of the feed (fore milk) and the second at the end of the feed (hind milk). The pantothenic acid in the milk was determined by microbiological assay using Lactobacillus plantarum, after prior treatment of the milk with intestinal phosphatase and pigeon liver extract to free bound pantothenic acid. There was no significance acid in the milk was 6.7 microgram/ml. No change occurred in the concentration of pantothenic acid in the milk from 1 to 6 months postpartum. There was a significant (p less than 0.005), positive correlation (r = 0.51) between the pantothenic acid in the diet of the mother the day preceding milk collection and the pantothenic acid content of the milk.

Adult↗

Radioimmunoassay for pantothenic acid in blood and other tissues.

We describe a radioimmunoassay for pantothenic acid in biological tissues. D-Pantothenic acid was conjugated with bovine serum albumin by use of a bromoacetyl derivative of pantothenic acid, and antibody to this antigen was raised by injecting it into the foot pads of rabbits. For the radioimmunoassay, a 100-fold dilution of the resulting antiserum was incubated with radiolabeled pantothentic acid. The antibodies were precipitated and dissolved, and the radioactivity of the solution was measured in a liquid scintillation counter. Between 5 and 125 ng of pantothenic acid can be detected in 75 muL of tissue extract. Validation included recovery and precision studies, parallelism with tissue extracts, and competitive binding studies. Results of the radioimmunoassay and those of microbiological assay with use of Lactobacillus plantarum correlated well (r = 0.80).

Aged↗

Amino acid-induced inhibition and stimulation of Saccharomyces carlsbergensis. I. Variations in the response to pantothenic acid induced by casein hydrolysate.

The response pattern of Saccharomyces carlsbergensis (ATCC 9080) to pantothenic acid in Atkin's medium was changed dramatically by adding small amounts of casein hydrolysate (0.032 to 0.32 mg/ml) to the assay medium. Under static, mildly anaerobic conditions, growth at low pantothenic acid levels was reduced by 54 to 69%, whereas at saturating or near saturating pantothenate concentrations marked stimulation of growth (up to 41%) was observed. Under aerobic conditions, inhibition but not stimulation of growth occurred. It is recommended that Atkin's medium for the assay of pantothenic acid with S. carlsbergensis (ATCC 9080) be modified to include 0.6% acid-hydrolyzed casein (Vitamin Free Casamino Acids, Difco) to prevent erroneous growth responses, which may result if significant amounts of amino acids are present in natural materials being assayed for this vitamin.

Amino Acids↗

Pantothenic acid, coenzyme A, and human chronic ulcerative and granulomatous colitis.

To investigate further an apparent relationship between chronic ulcerative and granulomatous colitis and pantothenic acid deficiency, colonic tissues obtained at the time of colectomy in 29 patients with these disorders were assayed for pantothenic acid and for coenzyme A (CoA) activity. For comparison, normal colonic tissues free of pathological lesions were obtained from 31 patients having colectomy for carcinoma or diverticulitis. Plasma, red blood cells, and colonic mucosa were assayed microbiologically for free and total pantothenic acid. The activity of CoA in colonic mucosa was determined by assaying the acetylation of sulfanilamide. Concentrations of free, bound, and total pantothenic acid in blood and in colonic mucosa did not differ between the two groups of patients. Bound pantothenic acid increased linearly with total pantothenic acid. Colonic mucosa concentrated free pantothenic acid to about 50 times the level of blood, and pantothenic acid in red cells was similar to the concentration in plasma. Compared to normal gut mucosa, CoA activity was markedly low in mucosa from patients with chronic ulcerative or granulomatous disease despite the presence of normal amounts of free and bound pantothenic acid. A block in the conversion of bound pantothenic acid to CoA in diseased mucosa is suggested.

Adult↗

Effects of supplemental pantothenic acid on wound healing: experimental study in rabbit.

The effect of pantothenic acid supplementation and deficiency on wound healing was investigated over a one month postoperative period in rabbits. The supplemented group was injected with pentothenate (20 mg/kg of body weight/24 h) for three weeks and compared to a placebo group (0.5 ml of distilled water). Deficient animals were fed with a pantothenate free diet also for three weeks. These three experimental groups were matched against a control group. The degree of wound healing was determined by the mean of postoperative breaking strength and wound fibroblast population changes. Pantothenic acid urinary excretion measured by gas chromatography served as control of pantothenate consumption. With regard to these three parameters no significant difference has been found between placebo and controls. The average urinary elimination in the pantothenic acid group was significantly higher as far as the pantothenate supplemented group was concerned, while the deficient group showed no significant decrease when compared to controls. Chronic pre- and postoperative pantothenic acid supplementation significantly increased aponeurosis strength after surgery; it improved slightly, but not significantly the strength of the skin. Furthermore, the fibroblast content of the scar became significantly greater during the fibroblast proliferation phase after pantothenic supplementation. These data suggest that pantothenic acid induces an accelerating effect of the normal healing process. The mechanism responsible for this improvement seems to be an increase in cellular multiplication during the first postoperative period. But the exact intimate mechanism of the beneficial effect of pantothenate remains unclear.

Animals↗

Interactions between ethanol and pantothenic acid on tremor and behavior in squirrel monkeys.

Ethanol consumption alters the levels and distribution of pantothenic acid and its metabolic products, an effect that can be counteracted by preloading with pantothenic acid. Ethanol also produces significant disturbances in motor function and has a potent tremorolytic activity when administered acutely. To investigate the interaction of pantothenic acid and ethanol, the two substances were administered alone and in combination to three squirrel monkeys trained to perform a response-initiated positioning task that enabled the detection of tremor. Tremor was evaluated using spectral analytical techniques. Ethanol at 1.0 gm/kg produced a tenfold reduction in tremor over control sessions while pantothenic acid alone had no effect on tremor. Pantothenic acid (200 mg/kg, IP or IV) administered before ethanol intubation completely counteracted the tremor-reducing action of ethanol in two monkeys and partially counteracted it in a third. The interaction between pantothenic acid and ethanol was limited to these motor effects; the rate-reducing effect of ethanol was unaffected by pantothenic acid.

Animals↗

Pantothenic acid status of adolescents.

Information on human needs for pantothenic acid is limited and no recommended daily allowance has been established, although a safe and adequate level of 4-7 mg/day has been suggested for adults and adolescents. Pantothenic acid levels in urine, whole blood, and erythrocytes were determined by radioimmunoassay in 63 healthy adolescents. Dietary intakes were calculated and evaluated from 4-day diet records. Although 49% of the females and 15% of the males consumed less than 4 mg/day, average blood levels for both groups were in a normal range relative to other populations (411.9 +/- 102.8 ng/mL and 344.5 +/- 113.6 ng/mL, respectively). Dietary intake was highly correlated with urinary excretion (p less than 0.001). Levels of pantothenic acid in erythrocytes correlated well with dietary intake and urinary excretion. A model was developed to predict circulating levels of pantothenic acid from dietary intake and urinary excretion.

Adolescent↗

Antimetabolites of pantothenic acid, ureido- and carbamoyl-derivatives.

Pantothenic acid analogs have been synthesized that contain alkyl and/or arylureido and carbamate functions in the beta-alanyl portion of the amide moiety of the vitamin. The analogs are inhibitory to growth of lactic acid bacteria at concentrations as low as 0.6 mug/ml, and the inhibitions are competitively reversed by supplements of pantothenic acid. The carbamate derivatives are more toxic to growth of Lactobacillus plantarum 8014 and Pediococcus cerevisiae 8042 than the ureido analogs, and chloro-substitutents on the aryl group significantly increase the toxicity of the analogs.

Bacteria↗

Absence of pantothenic acid in gramicidin S synthetase 2 obtained from some mutants of Bacillus brevis.

The pantothenic acid content of gramicidin S synthetase 2(GS 2) was estimated microbiologically with enzymes obtained from the wild strain and gramicidin S-lacking mutant strains of Bacillus brevis. Four mutant enzymes from BI-4, C-3, E-1, and E-2 lacked pantothenic acid. Other mutant enzymes from BII-3, BI-3, BI-9, and BI-2 contained the same amount of pantothenic acid as the wild-type enzyme. Pantothenic acid-lacking GS 2 belonged to group V of mutant enzymes, which could activate all amino acids related to gramicidin S; their complementary enzyme, gramicidin S synthetase 1(GS 1), lacked racemizing activity. To ascertain whether 4'-phosphopantetheine is involved in the formation of D-phenylalanyl-L-prolyl diketopiperazine (DKP) and gramicidin S, combinations were tested of intact GS 1 from the wild strain with various mutant GS 2 either containing or lacking pantothenic acid. Only the combinations of wild-type GS 1 with mutant GS 2 containing pantothenic acid could synthesize DKP. Combinations with pantothenic acid-lacking GS 2 also failed to elongate peptide chains. Pantothenic acid-lacking GS 2 could bind the four amino acids which constitute gramicidin S as acyladenylates and thioesters, but the binding abilities were lower than those of the wild-type enzyme and other mutant enzymes containing the pantothenic group.

Amino Acid Isomerases↗

Effects of pantothenic acid on postoperative adhesion formation in a rat uterine horn model.

This randomized blind study evaluated the effect of pantothenic acid on postoperative adhesion formation in euestrogenic and hypoestrogenic environment. We used the rat uterine horn model in a university-based laboratory setting. Thirty-six Sprague-Dawley rats were randomized into two estrogenic environments: euestrogenic and hypoestrogenic. The hypoestrogenic condition was achieved in 21 rats by either the administration of gonadotropin releasing hormone agonist or ovariectomy. The remaining 15 rats were untreated and remained in the regular estrogenic state. The left uterine horn was subjected to a lesion by serosal denudation at laparotomy. Following the uterine horn surgery, the rats within each environment were randomized into three treatment groups: saline (control), intraperitoneal pantothenic acid and intramuscular pantothenic acid. The degree of adhesions ten days following surgery was scored by an evaluated blinded to the rat's estrogenic condition and treatment. In the hypoestrogenic environment, there were no differences in the mean adhesions scores by treatment. In euestrogenic rats, the intraperitoneal pantothenic acid group had a higher mean adhesion score than intramuscular pantothenic acid, but neither treatment mean differed from that of the saline group. There was no difference in the mean adhesion scores of the saline groups by estrogenic environment. We concluded that pantothenic acid was not found to decrease adhesions formation when administered intraperitoneally or intramuscularly at these dosages. Contrary to previous reports, the hypoestrogenic condition alone was not found to be associated with decreased adhesion formation in our study.

Animals↗

Pantothenic acid deficiency detection in rainbow trout (Oncorhynchus mykiss).

Rainbow trout averaging 150 g were fed semipurified diets supplemented or not supplemented with pantothenic acid. After 16 wk of feeding, fish fed the deficient diet had reduced feed intake. At 28 wk, supplemented fish weighed > 600 g, whereas deficient fish weighed 425 g. Deficient fish became anorectic and listless at 25 wk and began to die at 28 wk. Histological examination of gill tissue revealed fused gill lamellae in the deficient fish, confirming pantothenic acid deficiency. At 4-wk intervals, samples of fish were taken from each group for determination of free and total concentrations of pantothenic acid in gills, liver, heart and erythrocytes by RIA. Concentrations of bound pantothenic acid, calculated by difference, did not differ between dietary treatment groups except in gills. Free pantothenic acid concentration in gills and heart were significantly lower in fish fed the deficient diet than in those fed the complete diet after 4 wk of feeding and remained so thereafter. Free pantothenic acid concentrations in the livers of deficient fish were significantly different from those in sufficient fish after 16 wk of feeding. Erythrocyte free pantothenic acid concentrations of deficient fish were significantly different from initial values at 8 wk and beyond. Using free pantothenic acid concentrations in erythrocytes allows detection of pantothenic acid deficiency in fish that are too valuable to permit destructive sampling techniques, such as broodstock and threatened or endangered species.

Animals↗

[Possible ways of regulating detoxifying processes in the alcohol dehydrogenase reaction with pantothenic acid derivatives].

Oxidation of derivatives and precursors of pantothenic acid was studied in alcohol dehydrogenase reactions. Despite the presence of free hydroxymethyl groups in a number of pantothenic acid derivatives only panthenol with Km = 8 x 10(-3) M was shown to serve as a substrate for alcohol dehydrogenase from horse liver tissue (EC 1.1.1.1) Pantethine, sodium phosphopantothenate, CoA and acetyl-CoA decreased the rate of ethanol oxidation, where pantethine and sodium phosphopantothenate were competitive inhibitors, while CoA and acetyl-CoA inhibited the enzyme noncompetitively Ki = 1.2 x 10(-2) M, 2.1 x 10(-2) M, 4.4 x 10(-4) M and 5.1 x 10(-4) M, respectively. Metabolic precursors, which were different from pantothenic acid in their structure, were not involved in the alcohol dehydrogenase reaction. Possible regulation of alcohol intoxication using derivatives and precursors of vitamin B3 is discussed.

Acetyl Coenzyme A↗

Glucoside formation as a novel metabolic pathway of pantothenic acid in the dog.

Metabolism of pantothenic acid (PaA) in beagle dogs was investigated. The dogs excreted 12.3% of the dose in the urine within 24 hr after a single oral administration of [3H]PaA (3 mg/kg). High performance liquid chromatographic analysis of the urine showed the presence of unchanged vitamin and a major metabolite, which accounted for 60.2 and 39.8% of the urinary radioactivity respectively. Although the metabolite was hydrolyzed by treatment with beta-glucuronidase or acid phosphatase, it was found that this hydrolysis resulted from the actions of beta-glucosidase contained as a contaminant in these enzyme preparations. beta-Glucosidase completely hydrolyzed the metabolite to generate PaA and glucose. The metabolite was isolated and subjected to GC/MS and NMR analyses. It was identical to synthetic PaA beta-glucoside, 4'-O-(beta-D-glucopyranosyl)-D-pantothenic acid. It was shown by the use of dog liver microsomes that PaA underwent beta-glucosidation in the presence of uridine diphosphate glucose (UDPG). It is proposed that beta-glucosidation by UDP-glucosyltransferase is a novel metabolic pathway of PaA in the dog.

Animals↗

Analytical studies on the chiral separation and simultaneous determination of pantothenic acid and hopantenic acid enantiomers in rat plasma by gas chromatography-mass fragmentography.

The chiral separation and simultaneous determination of D- and L-pantothenic acids and D- and L-hopantenic acids in rat plasma using gas chromatography-mass fragmentography are described. The method is based on deproteinization by ion-exchange resin, extraction with ethyl acetate under acidic conditions, and derivatization to form several interesting compounds. After methyl esterification for carboxylic acid of D- and L-pantothenic acids, D- and L-hopantenic acids could be derivatized to trifluoroacetate, cyclic sulphite, and cyclic n-butylboronate for hydroxy groups. D- and L-forms of these derivatives were completely separated by mass fragmentographic technique with quasi-molecular ions. Calcium salt of D-5-[(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)amino]pentanoic acid was used as an internal standard for the determination of DL-pantothenic acids and DL-hopantenic acids. The detection limits of DL-pantothenic acids and DL-hopantenic acids in this method were 5 and 12 ng, respectively. This method could be applied to the study of plasma levels of D-, L-pantothenic acids and D-, L-hopantenic acids in rat.

Animals↗