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The Journal of Investigative Dermatology Mar 2003Biotin is an essential micronutrient for normal cellular function, growth, and development. Biotin deficiency leads to pathologic, dermatologic, and neurocutaneous...
Biotin is an essential micronutrient for normal cellular function, growth, and development. Biotin deficiency leads to pathologic, dermatologic, and neurocutaneous manifestations in skin and its appendages. Previous studies described the presence of specific biotin transport systems in the epithelia of the intestine, liver, kidney, and placenta, and in blood mononuclear cells. The aim of this study was to examine biotin transport into human keratinocytes. Uptake of [3H]biotin was measured both in the HaCaT cell line and in native keratinocytes in primary culture. Uptake of [3H]biotin (6 nM) in HaCaT cells was linear for up to 5 min of incubation. In the presence of an Na+ gradient total biotin uptake was 4- to 5-fold higher than in the absence of sodium ions. Biotin uptake was not altered by H+ and Cl- gradients. This transport system exhibited a Michaelis-Menten constant for biotin of 22.7+/-1.0 microM and a maximal velocity of 163.6+/-3.5 pmol per 5 min per mg protein. [3H]Biotin uptake (6 nM) was strongly inhibited by lipoic acid (oxidized form, Ki=4.6 microM; reduced form, Ki=11.4 microM), pantothenic acid (Ki=1.2 microM), and desthiobiotin (Ki=15.2 microM), but not by biocytin or biotin methyl ester. Measured at [3H]biotin concentrations of 0.1-10 nM we obtained kinetic evidence for the presence of a second transport component that is saturable at very low biotin concentrations (Kt=2.6+/-0.1 nM). Unlabeled lipoic acid and pantothenic acid (20 nM) did not inhibit the [3H]biotin uptake (1 nM). We conclude that human keratinocytes express the Na+-dependent multivitamin transporter with preference for pantothenate and a very high affinity transport component with specificity for biotin.
Topics: Binding, Competitive; Biological Transport; Biotin; Cell Line; Humans; Keratinocytes; Kinetics; Pantothenic Acid; Sodium; Symporters
PubMed: 12603856
DOI: 10.1046/j.1523-1747.2003.12058.x -
British Journal of Experimental... Aug 1959
Topics: Animals; Disease; Duodenal Diseases; Duodenal Ulcer; Duodenitis; Duodenum; Pantothenic Acid; Peptic Ulcer; Rats; Vitamin B Deficiency
PubMed: 13799206
DOI: No ID Found -
Diverse biological activities of the vascular non-inflammatory molecules - the Vanin pantetheinases.Biochemical and Biophysical Research... Jan 2012The Vanin genes are a family that encode pantetheinases involved in recycling Coenzyme A, catalysing the breakdown of intermediate pantetheine to vitamin B5 for reuse in... (Review)
Review
The Vanin genes are a family that encode pantetheinases involved in recycling Coenzyme A, catalysing the breakdown of intermediate pantetheine to vitamin B5 for reuse in CoA biosynthesis. The role of pantetheinase in this most fundamental of cellular processes, was substantially characterised by the 1970s. The next 20 years saw little further interest in pantetheinase until various genetic studies implicated the Vanin locus in a range of normal and disease phenotypes, and a consequent interest in the other product of pantetheinase activity, cysteamine. This report seeks to bring together the early biochemical studies with recent biological data implicating cysteamine as a regulator of the oxidative state of a cell. Numerous studies now report a role for Vanin in inflammation, oxidative stress, cell migration and numerous diseases including cardiovascular disease.
Topics: Amidohydrolases; Amino Acid Sequence; Animals; Cardiovascular Diseases; Cell Membrane; Coenzyme A; GPI-Linked Proteins; Humans; Inflammation; Mice; Molecular Sequence Data; Pantetheine; Pantothenic Acid
PubMed: 22155241
DOI: 10.1016/j.bbrc.2011.11.099 -
Analytical Biochemistry Apr 2015Acyl-coenzyme A (CoA) thioesters are key metabolites in numerous anabolic and catabolic pathways, including fatty acid biosynthesis and β-oxidation, the Krebs cycle,...
Acyl-coenzyme A (CoA) thioesters are key metabolites in numerous anabolic and catabolic pathways, including fatty acid biosynthesis and β-oxidation, the Krebs cycle, and cholesterol and isoprenoid biosynthesis. Stable isotope dilution-based methodology is the "gold standard" for quantitative analyses by mass spectrometry. However, chemical synthesis of families of stable isotope-labeled metabolites such as acyl-CoA thioesters is impractical. Previously, we biosynthetically generated a library of stable isotope internal standard analogs of acyl-CoA thioesters by exploiting the essential requirement in mammals and insects for pantothenic acid (vitamin B5) as a metabolic precursor for the CoA backbone. By replacing pantothenic acid in the cell medium with commercially available [(13)C3(15)N1]-pantothenic acid, mammalian cells exclusively incorporated [(13)C3(15)N1]-pantothenate into the biosynthesis of acyl-CoA and acyl-CoA thioesters. We have now developed a much more efficient method for generating stable isotope-labeled CoA and acyl-CoAs from [(13)C3(15)N1]-pantothenate using stable isotope labeling by essential nutrients in cell culture (SILEC) in Pan6-deficient yeast cells. Efficiency and consistency of labeling were also increased, likely due to the stringently defined and reproducible conditions used for yeast culture. The yeast SILEC method greatly enhances the ease of use and accessibility of labeled CoA thioesters and also provides proof of concept for generating other labeled metabolites in yeast mutants.
Topics: Acyl Coenzyme A; Animals; Biosynthetic Pathways; Cell Culture Techniques; Cell Line, Tumor; Esters; Isotope Labeling; Mice; Pantothenic Acid; Saccharomyces cerevisiae
PubMed: 25572876
DOI: 10.1016/j.ab.2014.12.014 -
Poultry Science Sep 1993Two experiments were conducted with a commercial strain cross of 120 Large White British United Turkeys of America to determine the effect of pantothenic acid egg... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Two experiments were conducted with a commercial strain cross of 120 Large White British United Turkeys of America to determine the effect of pantothenic acid egg injections and dietary pantothenic acid on hatchability. The hens were housed individually in cages in a conventional house. In Experiment 1, three dietary treatments were used: 1) an unsupplemented practical corn-soybean meal basal diet; 2) the basal diet supplemented with 37.4 mg pantothenic acid/kg; and 3) the basal diet supplemented with 74.8 mg pantothenic acid/kg. Incremental dietary supplemental pantothenic acid levels increased the transfer of pantothenic acid in eggs, but did not result in a hatchability increase over the unsupplemented pantothenic acid basal diet. The response patterns from dietary pantothenic acid for the reproductive variables were similar whether the data were analyzed on a production period basis using all of the hens or on a subset of hens producing eggs in each production period. In Experiment 2, with hens fed 37.4 mg supplemental pantothenic acid/kg of diet, hatchability did not increase in eggs injected with 1,800 micrograms pantothenic acid per egg as compared with uninjected eggs and eggs injected with the vitamin carrier solution. The results of the study indicate that hatchability was not increased in turkey eggs from hens fed supplemental pantothenic acid or with egg pantothenic acid injections, which suggests that pantothenic acid is not limiting for hatchability in commercial turkey hen diets that contain 10.5 mg/kg or more of pantothenic acid.
Topics: Animal Nutritional Physiological Phenomena; Animals; Chick Embryo; Chickens; Female; Injections; Pantothenic Acid
PubMed: 8234134
DOI: 10.3382/ps.0721740 -
Journal of Clinical Hypertension... Jul 2022We aimed to evaluate the prospective association of vitamin B5 with all-cause mortality and explore its potential modifiers in Chinese adults with hypertension. A...
We aimed to evaluate the prospective association of vitamin B5 with all-cause mortality and explore its potential modifiers in Chinese adults with hypertension. A nested, case-control study was conducted in the China Stroke Primary Prevention Trial, including 505 deaths of all causes and 505 matched controls. The median follow-up duration was 4.5 years. The primary outcome measure in this investigation was all-cause mortality, which encompassed deaths for any reason. The mean plasma vitamin B5 concentration for cases (43.7 ng/mL) was higher than that in controls (40.9 ng/mL) (p = .001). When vitamin B5 was further assessed as quintiles, compared with the reference group (Q1: < 33.0 ng/mL), the risk of all-cause mortality increased by 29% (OR = 1.29, 95% CI: 0.83-2.01) in Q2, 22% (OR = 1.22, 95% CI: 0.77-1.94) in Q3, 62% (OR = 1.62, 95% CI: 1.00-2.62) in Q4, and 77% (OR = 1.77, 95% CI: 1.06-2.95) in Q5. The trend test was significant (p = .022). When Q4-Q5 were combined, a significant 41% increment (OR = 1.41, 95% CI: 1.03-1.95) in all-cause death risk was found compared with Q1-Q3. The adverse effects were more pronounced in those with normal folate levels (p-interaction = .019) and older people (p-interaction = .037). This study suggests that higher baseline levels of plasma vitamin B5 are a risk factor for all-cause mortality among Chinese patients with hypertension, especially among older adults and those with adequate folate levels. The findings, if confirmed, may inform novel clinical and nutritional guidelines and interventions to optimize vitamin B5 levels.
Topics: Aged; Case-Control Studies; Folic Acid; Humans; Hypertension; Pantothenic Acid; Risk Factors
PubMed: 35699663
DOI: 10.1111/jch.14516 -
Journal of Proteome Research Sep 2009Activation of the peroxisome proliferator-activated receptor alpha (PPARalpha) is associated with increased fatty acid catabolism and is commonly targeted for the...
Activation of the peroxisome proliferator-activated receptor alpha (PPARalpha) is associated with increased fatty acid catabolism and is commonly targeted for the treatment of hyperlipidemia. To identify latent, endogenous biomarkers of PPARalpha activation and hence increased fatty acid beta-oxidation, healthy human volunteers were given fenofibrate orally for 2 weeks and their urine was profiled by UPLC-QTOFMS. Biomarkers identified by the machine learning algorithm random forests included significant depletion by day 14 of both pantothenic acid (>5-fold) and acetylcarnitine (>20-fold), observations that are consistent with known targets of PPARalpha including pantothenate kinase and genes encoding proteins involved in the transport and synthesis of acylcarnitines. It was also concluded that serum cholesterol (-12.7%), triglycerides (-25.6%), uric acid (-34.7%), together with urinary propylcarnitine (>10-fold), isobutyrylcarnitine (>2.5-fold), (S)-(+)-2-methylbutyrylcarnitine (5-fold), and isovalerylcarnitine (>5-fold) were all reduced by day 14. Specificity of these biomarkers as indicators of PPARalpha activation was demonstrated using the Ppara-null mouse. Urinary pantothenic acid and acylcarnitines may prove useful indicators of PPARalpha-induced fatty acid beta-oxidation in humans. This study illustrates the utility of a pharmacometabolomic approach to understand drug effects on lipid metabolism in both human populations and in inbred mouse models.
Topics: Adult; Algorithms; Analysis of Variance; Animals; Artificial Intelligence; Biomarkers; Carnitine; Chromatography, High Pressure Liquid; Fatty Acids; Female; Fenofibrate; Humans; Hypolipidemic Agents; Male; Mass Spectrometry; Metabolome; Metabolomics; Mice; Mice, Inbred C57BL; PPAR alpha; Pantothenic Acid; Urine
PubMed: 19569716
DOI: 10.1021/pr9004103 -
Molecules (Basel, Switzerland) Mar 2022Curcumin (CUR) and D-panthenol (DPA) have been widely investigated for wound-healing treatment. In order to analyse these two compounds from a dosage form, such as...
Curcumin (CUR) and D-panthenol (DPA) have been widely investigated for wound-healing treatment. In order to analyse these two compounds from a dosage form, such as polymer-based wound dressings or creams, an analytical method that allows the quantification of both drugs simultaneously should be developed. Here, we report for the first time a validated high-performance liquid chromatographic (HPLC) method coupled with UV detection to quantify CUR and DPA based on the standards set by the International Council on Harmonization (ICH) guidelines. The separation of the analytes was performed using a C column that utilised a mobile phase consisting of 0.001% / phosphoric acid and methanol using a gradient method with a run time of 15 min. The method is linear for drug concentrations within the range of 0.39-12.5 μg mL (R = 0.9999) for CUR and 0.39-25 μg mL for DPA (R = 1). The validated method was found to be precise and accurate. Moreover, the CUR and DPA solution was found to be stable under specific storage conditions. We, therefore, suggest that the HPLC-UV method developed in this study may be very useful in screening formulations for CUR and DPA within a preclinical setting through in vitro release studies.
Topics: Bandages; Chromatography, High Pressure Liquid; Curcumin; Pantothenic Acid
PubMed: 35335123
DOI: 10.3390/molecules27061759 -
Determination of pantothenic acid in infant milk formulas by high performance liquid chromatography.Journal of Dairy Science Apr 1996A reverse-phase liquid chromatographic method was adapted for the assay of pantothenic acid in infant milk formulas. Sample preparation consisted of deproteination with... (Comparative Study)
Comparative Study
A reverse-phase liquid chromatographic method was adapted for the assay of pantothenic acid in infant milk formulas. Sample preparation consisted of deproteination with acetic acid and sodium acetate solutions, followed by centrifugation and filtration. The chromatographic system included a C-18 column and a mobile phase consisting of a sodium phosphate buffer and acetonitrile (97:3, vol/vol). The column effluent was monitored by UV detection at 197 nm. The system was linear from 50 to 800 ng. The recoveries of pantothenic acid from augmented samples ranged from 89 to 98%, and the coefficients of variation ranged from 1.17 to 3.20%. The results obtained with the HPLC and a microbiological method were highly correlated for starting infant formula, follow-up infant formula, and formula for infants of low birth weight from four different manufactures. All formulas analyzed contained pantothenic acid at concentrations higher than those declared on their nutritional labels and were in compliance with international recommendations.
Topics: Chromatography, High Pressure Liquid; Drug Stability; Food Labeling; Humans; Infant; Infant Food; Pantothenic Acid; Sensitivity and Specificity
PubMed: 8744215
DOI: 10.3168/jds.S0022-0302(96)76394-4 -
Journal of Bacteriology Dec 1981Coenzyme A (CoA) and acyl carrier protein are two cofactors in fatty acid metabolism, and both possess a 4'-phosphopantetheine moiety that is metabolically derived from...
Coenzyme A (CoA) and acyl carrier protein are two cofactors in fatty acid metabolism, and both possess a 4'-phosphopantetheine moiety that is metabolically derived from the vitamin pantothenate. We studied the regulation of the metabolic pathway that gives rise to these two cofactors in an Escherichia coli beta-alanine auxotroph, strain SJ16. Identification and quantitation of the intracellular and extracellular beta-alanine-derived metabolites from cells grown on increasing beta-alanine concentrations were performed. The intracellular content of acyl carrier protein was relatively insensitive to beta-alanine input, whereas the CoA content increased as a function of external beta-alanine concentration, reaching a maximum at 8 microM beta-alanine. Further increase in the beta-alanine concentration led to the excretion of pantothenate into the medium. Comparing the amount of pantothenate found outside the cell to the level of intracellular metabolites demonstrates that E. coli is capable of producing 15-fold more pantoic acid than is required to maintain the intracellular CoA content. Therefore, the supply of pantoic acid is not a limiting factor in CoA biosynthesis. Wild-type cells also excreted pantothenate into the medium, showing that the beta-alanine supply is also not rate limiting in CoA biogenesis. Taken together, the results point to pantothenate kinase as the primary enzymatic step that regulates the CoA content of E. coli.
Topics: Acyl Carrier Protein; Coenzyme A; Escherichia coli; Organophosphorus Compounds; Pantetheine; Pantothenic Acid; beta-Alanine
PubMed: 6796563
DOI: 10.1128/jb.148.3.926-932.1981