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| Pantothenic acid (vitamin B5) is a B vitamin and an essential nutrient. All animals need pantothenic acid in order to synthesize coenzyme A (CoA), which is essential for cellular energy production and for the synthesis and degradation of proteins, carbohydrates, and fats.
Pantothenic acid is the combination of pantoic acid and β-alanine. Its name comes from the Greek πάντοθεν pantothen, meaning "from everywhere", because pantothenic acid, at least in small amounts, is in almost all foods. Deficiency of pantothenic acid is very rare in humans. In dietary supplements and animal feed, the form commonly used is calcium pantothenate, because chemically it is more stable, and hence makes for longer product shelf-life, than sodium pantothenate and free pantothenic acid. |
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Read full article at Wikipedia
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InChI=1S/C9H17NO5/c1- 9(2,5-11)7(14)8(15)10-4-3-6(12)13/h7,11,14H,3-5H2,1-2H3,(H,10,15)(H,12,13)/t7-/m0/s1 |
| GHOKWGTUZJEAQD-ZETCQYMHSA-N |
| CC(C)(CO)[C@@H](O)C(=O)NCCC(O)=O |
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Chlamydomonas reinhardtii
(NCBI:txid3055)
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From MetaboLights
See:
MetaboLights Study
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Chlamydomonas reinhardtii
(NCBI:txid3055)
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From MetaboLights
See:
MetaboLights Study
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Glycine max
(NCBI:txid3847)
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From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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Found in
blood serum
(BTO:0000133).
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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Found in
blood serum
(BTO:0000133).
From MetaboLights
See:
MetaboLights Study
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Homo sapiens
(NCBI:txid9606)
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Found in
blood serum
(BTO:0000133).
From MetaboLights
See:
MetaboLights Study
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human blood serum metabolite
Any metabolite (endogenous or exogenous) found in human blood serum samples.
water-soluble vitamin (role)
Any vitamin that dissolves in water and readily absorbed into tissues for immediate use. Unlike the fat-soluble vitamins, they are not stored in the body and need to be replenished regularly in the diet and will rarely accumulate to toxic levels since they are quickly excreted from the body via urine.
(via B vitamin )
(via pantothenic acids )
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
(via pantothenic acid )
cofactor
An organic molecule or ion (usually a metal ion) that is required by an enzyme for its activity. It may be attached either loosely (coenzyme) or tightly (prosthetic group).
(via pantothenic acids )
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antidote to curare poisoning
A role borne by a molecule that acts to counteract or neutralize the deleterious effects of curare.
geroprotector
Any compound that supports healthy aging, slows the biological aging process, or extends lifespan.
nutraceutical
A product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
(via B vitamin )
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View more via ChEBI Ontology
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3-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanoic acid
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(+)-Pantothenic acid
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HMDB
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(R)-N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)-β-alanine
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ChemIDplus
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chick antidermatitis factor
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ChemIDplus
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D(+)-N-(2,4-dihydroxy-3,3-dimethylbutyryl)-β-alanine
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ChemIDplus
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D-(+)-pantothenic acid
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ChEBI
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D-pantothenic acid
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ChemIDplus
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N-[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]-beta-alanine
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PDBeChem
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Pantothenic acid
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KEGG COMPOUND
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PANTOTHENOIC ACID
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PDBeChem
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vitamin B5
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ChemIDplus
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1727064
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Beilstein Registry Number
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ChemIDplus
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1727064
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Reaxys Registry Number
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Reaxys
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79-83-4
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CAS Registry Number
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NIST Chemistry WebBook
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79-83-4
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CAS Registry Number
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ChemIDplus
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Zou SP, Wang ZJ, Zhao K, Zhang B, Niu K, Liu ZQ, Zheng YG (2021)
High-level production of d-pantothenic acid from glucose by fed-batch cultivation of Escherichia coli.
Biotechnology and applied biochemistry 68, 1227-1235 [PubMed:32979277]
[show Abstract]
d-Pantothenic acid (D-PA) is an essential vitamin widely used in food, feed, chemical, and pharmaceutical industries. An Escherichia coli platform was developed for the high-level production of D-PA from glucose through fed-batch cultivation. Initially, the effects of different glucose feeding strategies D-PA synthesis were studied. It was found that D-PA production in glucose control (5 g/L) fed-batch culture reached 24.3 g/L, which was 4.09 times that in the batch culture. Next, the effect of auxotrophic amino acid (isoleucine)-limited feeding on D-PA production was investigated. The results revealed that isoleucine feeding decreased the accumulation of by-product acetic acid and promoted D-PA production significantly. Furthermore, an isoleucine feeding embedded multistage glucose supply strategy was established, and a maximum titer of 39.1 g/L was achieved. To the best of our knowledge, this levels are the highest reported so far in engineered E. coli for the D-PA production. The developed fed-batch feeding strategy may be useful for the industrial D-PA production by E. coli. | Xu J, Patassini S, Begley P, Church S, Waldvogel HJ, Faull RLM, Unwin RD, Cooper GJS (2020)
Cerebral deficiency of vitamin B5 (d-pantothenic acid; pantothenate) as a potentially-reversible cause of neurodegeneration and dementia in sporadic Alzheimer's disease.
Biochemical and biophysical research communications 527, 676-681 [PubMed:32416962]
[show Abstract]
Alzheimer's disease (AD) is the most common cause of age-related neurodegeneration and dementia, and there are no available treatments with proven disease-modifying actions. It is therefore appropriate to study hitherto-unknown aspects of brain structure/function in AD to seek alternative disease-related mechanisms that might be targeted by new therapeutic interventions with disease-modifying actions. During hypothesis-generating metabolomic studies of brain, we identified apparent differences in levels of vitamin B5 between AD cases and controls. We therefore developed a method based on gas chromatography-mass spectrometry by which we quantitated vitamin B5 concentrations in seven brain regions from nine AD cases and nine controls. We found that widespread, severe cerebral deficiency of vitamin B5 occurs in AD. This deficiency was worse in those regions known to undergo severe damage, including the hippocampus, entorhinal cortex, and middle temporal gyrus. Vitamin B5 is the obligate precursor of CoA/acetyl-CoA (acetyl-coenzyme A), which plays myriad key roles in the metabolism of all organs, including the brain. In brain, acetyl-CoA is the obligate precursor of the neurotransmitter acetylcholine, and the complex fatty-acyl groups that mediate the essential insulator role of myelin, both processes being defective in AD; moreover, the large cerebral vitamin B5 concentrations co-localize almost entirely to white matter. Vitamin B5 is well tolerated when administered orally to humans and other mammals. We conclude that cerebral vitamin B5 deficiency may well cause neurodegeneration and dementia in AD, which might be preventable or even reversible in its early stages, by treatment with suitable oral doses of vitamin B5. | Subramanian C, Yun MK, Yao J, Sharma LK, Lee RE, White SW, Jackowski S, Rock CO (2016)
Allosteric Regulation of Mammalian Pantothenate Kinase.
The Journal of biological chemistry 291, 22302-22314 [PubMed:27555321]
[show Abstract]
Pantothenate kinase is the master regulator of CoA biosynthesis and is feedback-inhibited by acetyl-CoA. Comparison of the human PANK3·acetyl-CoA complex to the structures of PANK3 in four catalytically relevant complexes, 5'-adenylyl-β,γ-imidodiphosphate (AMPPNP)·Mg2+, AMPPNP·Mg2+·pantothenate, ADP·Mg2+·phosphopantothenate, and AMP phosphoramidate (AMPPN)·Mg2+, revealed a large conformational change in the dimeric enzyme. The amino-terminal nucleotide binding domain rotates to close the active site, and this allows the P-loop to engage ATP and facilitates required substrate/product interactions at the active site. Biochemical analyses showed that the transition between the inactive and active conformations, as assessed by the binding of either ATP·Mg2+ or acyl-CoA to PANK3, is highly cooperative indicating that both protomers move in concert. PANK3(G19V) cannot bind ATP, and biochemical analyses of an engineered PANK3/PANK3(G19V) heterodimer confirmed that the two active sites are functionally coupled. The communication between the two protomers is mediated by an α-helix that interacts with the ATP-binding site at its amino terminus and with the substrate/inhibitor-binding site of the opposite protomer at its carboxyl terminus. The two α-helices within the dimer together with the bound ligands create a ring that stabilizes the assembly in either the active closed conformation or the inactive open conformation. Thus, both active sites of the dimeric mammalian pantothenate kinases coordinately switch between the on and off states in response to intracellular concentrations of ATP and its key negative regulators, acetyl(acyl)-CoA. | Shibata K, Kaneko M, Fukuwatari T (2013)
D-pantethine has vitamin activity equivalent to d-pantothenic acids for recovering from a deficiency of D-pantothenic acid in rats.
Journal of nutritional science and vitaminology 59, 93-99 [PubMed:23727638]
[show Abstract]
D-Pantethine is a compound in which two molecules of D-pantetheine bind through an S-S linkage. D-Pantethine is available from commercial sources as well as from D-pantothenic acid. We investigated if D-pantethine has the same vitamin activity as D-pantothenic acid by comparing the recovery from a deficiency of D-pantothenic acid in rats. D-Pantothenic acid-deficient rats were developed by weaning rats on a diet lacking D-pantothenic acid for 47 d. At that time, the urinary excretion of D-pantothenic acid was almost zero, and the body weight extremely low, compared with the control (p<0.05); the contents of free D-pantothenic acid were also significantly reduced in comparison with those of controls (p<0.05). D-Pantothenic acid-deficient rats were administered a diet containing D-pantothenic acid or D-pantethine for 7 d. D-Pantethine and D-pantothenic acid contents of the diets were equimolar in forms of D-pantothenic acid. We compared various parameters concerning nutritional status between rats fed D-pantothenic acid- and D-pantethine-containing diets. The recoveries of body weight, tissue weights, and tissue concentrations of free D-pantothenic acid, dephospho-CoA, CoA, and acetyl-CoA were identical between rats fed diets containing D-pantothenic acid and D-pantethine. Thus, the biological efficiency for recovering from a deficiency of D-pantothenic acid in rats was equivalent between D-pantothenic acid and D-pantethine. | Andrieux P, Fontannaz P, Kilinc T, Giménez EC (2012)
Pantothenic acid (vitamin B5) in fortified foods: comparison of a novel ultra-performance liquid chromatography-tandem mass spectrometry method and a microbiological assay (AOAC Official Method 992.07).
Journal of AOAC International 95, 143-148 [PubMed:22468352]
[show Abstract]
A novel method was developed and single-laboratory validated for the determination of free pantothenic acid (vitamin B5) in a wide range of infant and adult fortified food products. The method combines simple sample preparation and chromatographic analysis using ultra-performance LC coupled to tandem MS with positive electrospray ionization. Pantothenic acid was quantified using [13C6, 15N2]-pantothenic acid as an internal standard. Calibration curves were linear between 0.08 and 1.2 microg/mL (r2 = 0.9998), and average recovery varied between 95 and 106%. The method exhibited overall RSD(r) of 1.1% and RSD intermediate reproducibility from 2.5 to 6.0% in infant formulas and cereals. Comparison of results between total and free pantothenic acid showed that the analysis of free pantothenic acid gave a good estimation of total pantothenic acid in the range of products analyzed. The method provides reliable free pantothenic acid results in a wide range of fortified foods (infant and adult nutritionals, cereal products and beverages), and shows good correlation with the microbiological method AOAC Official Method 992.07. It is a more selective, faster, and robust alternative to microbiological determination. | Wall BT, Stephens FB, Marimuthu K, Constantin-Teodosiu D, Macdonald IA, Greenhaff PL (2012)
Acute pantothenic acid and cysteine supplementation does not affect muscle coenzyme A content, fuel selection, or exercise performance in healthy humans.
Journal of applied physiology (Bethesda, Md. : 1985) 112, 272-278 [PubMed:22052867]
[show Abstract]
Reduced skeletal muscle free coenzyme A (CoASH) availability may decrease the contribution of fat oxidation to ATP production during high-intensity, submaximal exercise or, alternatively, limit pyruvate dehydrogenase complex (PDC) flux and thereby carbohydrate oxidation. Here we attempted to increase the muscle CoASH pool in humans, via pantothenic acid and cysteine feeding, in order to elucidate the role of CoASH availability on muscle fuel metabolism during exercise. On three occasions, eight healthy male volunteers (age 22.9 ± 1.4 yr, body mass index 24.2 ± 1.5 kg/m(2)) cycled at 75% maximal oxygen uptake (Vo(2max)) to exhaustion, followed by a 15-min work output performance test. Muscle biopsies were obtained at rest, and after 60 min and 91.3 ± 3.1 min of exercise (time to exhaustion on baseline visit) on each occasion. Two weeks following the first visit (baseline), 1 wk of oral supplementation with either 3 g/day of a placebo control (glucose polymer; CON) or 1.5 g/day each of d-pantothenic acid and l-cysteine (CP) was carried out prior to the second and third visits in a randomized, counterbalanced, double-blind manner, leaving a 3-wk gap in total between each visit. Resting muscle CoASH content was not altered by supplementation in any visit. Following 60 min of exercise, muscle CoASH content was reduced by 13% from rest in all three visits (P < 0.05), and similar changes in the respiratory exchange ratio, glycogenolysis (∼235 mmol/kg dry muscle), PCr degradation (∼57 mmol/kg dry muscle), and lactate (∼25 mmol/kg dry muscle) and acetylcarnitine (∼12 mmol(.)kg/dry muscle) accumulation was observed during exercise when comparing visits. Furthermore, no difference in work output was observed when comparing CON and CP. Acute feeding with pantothenic acid and cysteine does not alter muscle CoASH content and consequently does not impact on muscle fuel metabolism or performance during exercise in humans. | Chetnani B, Kumar P, Abhinav KV, Chhibber M, Surolia A, Vijayan M (2011)
Location and conformation of pantothenate and its derivatives in Mycobacterium tuberculosis pantothenate kinase: insights into enzyme action.
Acta crystallographica. Section D, Biological crystallography 67, 774-783 [PubMed:21904030]
[show Abstract]
Previous studies of complexes of Mycobacterium tuberculosis PanK (MtPanK) with nucleotide diphosphates and nonhydrolysable analogues of nucleoside triphosphates in the presence or the absence of pantothenate established that the enzyme has dual specificity for ATP and GTP, revealed the unusual movement of ligands during enzyme action and provided information on the effect of pantothenate on the location and conformation of the nucleotides at the beginning and the end of enzyme action. The X-ray analyses of the binary complexes of MtPanK with pantothenate, pantothenol and N-nonylpantothenamide reported here demonstrate that in the absence of nucleotide these ligands occupy, with a somewhat open conformation, a location similar to that occupied by phosphopantothenate in the `end' complexes, which differs distinctly from the location of pantothenate in the closed conformation in the ternary `initiation' complexes. The conformation and the location of the nucleotide were also different in the initiation and end complexes. An invariant arginine appears to play a critical role in the movement of ligands that takes place during enzyme action. The work presented here completes the description of the locations and conformations of nucleoside diphosphates and triphosphates and pantothenate in different binary and ternary complexes, and suggests a structural rationale for the movement of ligands during enzyme action. The present investigation also suggests that N-alkylpantothenamides could be phosphorylated by the enzyme in the same manner as pantothenate. | Chetnani B, Kumar P, Surolia A, Vijayan M (2010)
M. tuberculosis pantothenate kinase: dual substrate specificity and unusual changes in ligand locations.
Journal of molecular biology 400, 171-185 [PubMed:20451532]
[show Abstract]
Kinetic measurements of enzyme activity indicate that type I pantothenate kinase from Mycobacterium tuberculosis has dual substrate specificity for ATP and GTP, unlike the enzyme from Escherichia coli, which shows a higher specificity for ATP. A molecular explanation for the difference in the specificities of the two homologous enzymes is provided by the crystal structures of the complexes of the M. tuberculosis enzyme with (1) GMPPCP and pantothenate, (2) GDP and phosphopantothenate, (3) GDP, (4) GDP and pantothenate, (5) AMPPCP, and (6) GMPPCP, reported here, and the structures of the complexes of the two enzymes involving coenzyme A and different adenyl nucleotides reported earlier. The explanation is substantially based on two critical substitutions in the amino acid sequence and the local conformational change resulting from them. The structures also provide a rationale for the movement of ligands during the action of the mycobacterial enzyme. Dual specificity of the type exhibited by this enzyme is rare. The change in locations of ligands during action, observed in the case of the M. tuberculosis enzyme, is unusual, so is the striking difference between two homologous enzymes in the geometry of the binding site, locations of ligands, and specificity. Furthermore, the dual specificity of the mycobacterial enzyme appears to have been caused by a biological necessity. | Chetnani B, Das S, Kumar P, Surolia A, Vijayan M (2009)
Mycobacterium tuberculosis pantothenate kinase: possible changes in location of ligands during enzyme action.
Acta crystallographica. Section D, Biological crystallography 65, 312-325 [PubMed:19307712]
[show Abstract]
The crystal structures of complexes of Mycobacterium tuberculosis pantothenate kinase with the following ligands have been determined: (i) citrate; (ii) the nonhydrolysable ATP analogue AMPPCP and pantothenate (the initiation complex); (iii) ADP and phosphopantothenate resulting from phosphorylation of pantothenate by ATP in the crystal (the end complex); (iv) ATP and ADP, each with half occupancy, resulting from a quick soak of crystals in ATP (the intermediate complex); (v) CoA; (vi) ADP prepared by soaking and cocrystallization, which turned out to have identical structures, and (vii) ADP and pantothenate. Solution studies on CoA binding and catalytic activity have also been carried out. Unlike in the case of the homologous Escherichia coli enzyme, AMPPCP and ADP occupy different, though overlapping, locations in the respective complexes; the same is true of pantothenate in the initiation complex and phosphopantothenate in the end complex. The binding site of MtPanK is substantially preformed, while that of EcPanK exhibits considerable plasticity. The difference in the behaviour of the E. coli and M. tuberculosis enzymes could be explained in terms of changes in local structure resulting from substitutions. It is unusual for two homologous enzymes to exhibit such striking differences in action. Therefore, the results have to be treated with caution. However, the changes in the locations of ligands exhibited by M. tuberculosis pantothenate kinase are remarkable and novel. | YAMAMOTO T, JAROENPORN S, PAN L, AZUMANO I, ONDA M, NAKAMURA K, WATANABE G, TAYA K (2009)
Effects of pantothenic acid on testicular function in male rats.
The Journal of veterinary medical science 71, 1427-1432 [PubMed:19959891]
[show Abstract]
Pantothenic acid (PaA) is a water-soluble vitamin required to sustain various physiological functions in animals. The physiological roles of PaA on testicular function, in particular, testicular endocrinology and sperm mortility, were investigated in rats. Male rats at 3 weeks of age were fed a PaA-free diet or a 0.0016% PaA diet (control) for 7 weeks. Total body weight, as well as the weights of the liver, kidney, pituitary, testis, epididymis, seminal vesicle and prostate; sperm motility; and the plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and corticosterone were measured in rats at 10 weeks of age. Body weight gain decreased from 5 weeks of age in rats fed the PaA-free diet compared with the control. The relative weights of the testes were significantly higher in the PaA-deficient group compared with the control group. Several parameters of sperm motility were significantly reduced in the PaA-deficient group compared with the control group. In addition, the plasma concentrations of testosterone and corticosterone were significantly lower in the PaA-deficient group compared with the control group, whereas the plasma concentrations of FSH and LH showed no change. These results clearly demonstrate that PaA is an essential factor in testicular endocrinology and sperm motility in male rats. | Yang K, Strauss E, Huerta C, Zhang H (2008)
Structural basis for substrate binding and the catalytic mechanism of type III pantothenate kinase.
Biochemistry 47, 1369-1380 [PubMed:18186650]
[show Abstract]
Pantothenate kinase (PanK) catalyzes the first step of the universal five-step coenzyme A (CoA) biosynthetic pathway. The recently characterized type III PanK (PanK-III, encoded by the coaX gene) is distinct in sequence, structure and enzymatic properties from both the long-known bacterial type I PanK (PanK-I, exemplified by the Escherichia coli CoaA protein) and the predominantly eukaryotic type II PanK (PanK-II). PanK-III enzymes have an unusually high Km for ATP, are resistant to feedback inhibition by CoA, and are unable to utilize the N-alkylpantothenamide family of pantothenate analogues as alternative substrates, thus making type III PanK ineffective in generating CoA analogues as antimetabolites in vivo. Previously, we reported the crystal structure of the PanK-III from Thermotoga maritima and identified it as a member of the "acetate and sugar kinase/heat shock protein 70/actin" (ASKHA) superfamily. Here we report the crystal structures of the same PanK-III in complex with one of its substrates (pantothenate), its product (phosphopantothenate) as well as a ternary complex structure of PanK-III with pantothenate and ADP. These results are combined with isothermal titration calorimetry experiments to present a detailed structural and thermodynamic characterization of the interactions between PanK-III and its substrates ATP and pantothenate. Comparison of substrate binding and catalytic sites of PanK-III with that of eukaryotic PanK-II revealed drastic differences in the binding modes for both ATP and pantothenate substrates, and suggests that these differences may be exploited in the development of new inhibitors specifically targeting PanK-III. | Castrillo JI, Zeef LA, Hoyle DC, Zhang N, Hayes A, Gardner DC, Cornell MJ, Petty J, Hakes L, Wardleworth L, Rash B, Brown M, Dunn WB, Broadhurst D, O'Donoghue K, Hester SS, Dunkley TP, Hart SR, Swainston N, Li P, Gaskell SJ, Paton NW, Lilley KS, Kell DB, Oliver SG (2007)
Growth control of the eukaryote cell: a systems biology study in yeast.
Journal of biology 6, 4 [PubMed:17439666]
[show Abstract]
BackgroundCell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking.ResultsMetabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth.ConclusionThis work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell. | Schittl H, Getoff N (2007)
Radiation-induced antitumor properties of vitamin B5 (pantothenic acid) and its effect on mitomycin C activity: experiments in vitro.
Oncology research 16, 389-394 [PubMed:17913047]
[show Abstract]
Vitamin B5 (pantothenic acid) shows a strongly pronounced antitumor effect under the influence of ionizing radiation. In the frame of experiments in vitro (model: Escherichia coli bacteria, AB1157) performed under the exact knowledge of concentration and kind of the free radicals acting in the various aqueous media (pH 7.4) the following was established: (i) vitamin B5 possesses a very intense antitumor property, (ii) it exerts a strong synergistic effect on mitomycin C (MMC), (iii) the oxidizing species (OH*, O2*-) appears to be most important in the initiation of the observed effect. The generated radiolytic products from vitamin B5 very likely also play an important role in this respect. | Coxon KM, Chakauya E, Ottenhof HH, Whitney HM, Blundell TL, Abell C, Smith AG (2005)
Pantothenate biosynthesis in higher plants.
Biochemical Society transactions 33, 743-746 [PubMed:16042590]
[show Abstract]
Pantothenate (vitamin B5) is a water-soluble vitamin essential for the synthesis of CoA and ACP (acyl-carrier protein, cofactors in energy yielding reactions including carbohydrate metabolism and fatty acid synthesis. Pantothenate is synthesized de novo by plants and micro-organisms; however, animals obtain the vitamin through their diet. Utilizing our knowledge of the pathway in Escherichia coli, we have discovered and cloned genes encoding the first and last enzymes of the pathway from Arabidopsis, panB1, panB2 and panC. It is unlikely that there is a homologue of the E. coli panD gene, therefore plants must make beta-alanine by an alternative route. Possible candidates for the remaining gene, panE, are being investigated. GFP (green fluorescent protein) fusions of the three identified plant enzymes have been generated and the subcellular localization of the enzymes studied. Work is now being performed to elucidate expression patterns of the transcripts and characterize the proteins encoded by these genes. | Heudi O, Fontannaz P (2005)
Determination of vitamin B5 in human urine by high-performance liquid chromatography coupled with mass spectrometry.
Journal of separation science 28, 669-672 [PubMed:15912738]
[show Abstract]
In the present work, we have developed a simple and rapid liquid chromatography/mass spectrometry (LC/MS) method for the identification and quantification of vitamin B5 in human urine. Urine was spiked with vitamin B5 internal standard, hopantenic acid (HOPA), and then diluted with the LC mobile phase prior to its analysis by LC/MS. The quantification was performed in single ion monitoring mode. The calibration curve was linear (r2 = 0.999) between 0.25 to 10 microg/mL. With a limit of detection of 0.1 microg/mL the method was sensitive enough to determine low levels of vitamin B5 in urine. The overall quantitative efficiency of the method was evaluated by spiking urine samples with four different concentrations of vitamin B5; the intra-assay coefficient of variation was below 5% and the recoveries were between 96 to 108%. The results of the present study show that the proposed method is selective and sensitive enough for the quantification of vitamin B5 in urine. | Mittermayr R, Kalman A, Trisconi MJ, Heudi O (2004)
Determination of vitamin B5 in a range of fortified food products by reversed-phase liquid chromatography-mass spectrometry with electrospray ionisation.
Journal of chromatography. A 1032, 1-6 [PubMed:15065769]
[show Abstract]
Methods for Vitamin B5 determination in food products remain limited by their low sensitivity and poor selectivity. Here, we have developed a liquid chromatography-mass spectrometry (LC-MS) method for Vitamin B5 determination in wide range of fortified food products. Vitamin B5 was extracted from food samples by heat treatment and analysed by LC-MS in the positive mode using electrospray ionisation (ESI). Vitamin B5 was quantified using hopantenic acid (HOPA) as internal standard after their separation on a C18 narrow-bore column with a gradient of mobile phase made of water/acetonitrile and trifluoroacetic acid (TFA) 0.025%. MS with single ion monitoring mode at mass m/z 220 was used for Vitamin B5 quantification. Calibration curve between 0.5 and 10 microg/ml of Vitamin B5 was linear (r2=0.9993) and the detection limit was determined to be 800 pg. The overall quantitative efficiency of the method was evaluated using Nestle reference sample (infant formula). The intra-assay RSD was 4.8% (n=8), the inter-assay RSD 6.4% (n=4) and the recoveries of the spiked samples were above 95%. Application of the LC-MS method to Vitamin B5 determination in wide range of fortified food products including three US National Institute of Standards and Technology (NIST) reference samples (RM 8435, RM 8415 and SRM 1546) shows consistent results with those obtained by microbiology and recoveries of Vitamin B5 between 93 and 104% for the spiked samples. | Ivey RA, Zhang YM, Virga KG, Hevener K, Lee RE, Rock CO, Jackowski S, Park HW (2004)
The structure of the pantothenate kinase.ADP.pantothenate ternary complex reveals the relationship between the binding sites for substrate, allosteric regulator, and antimetabolites.
The Journal of biological chemistry 279, 35622-35629 [PubMed:15136582]
[show Abstract]
Pantothenate kinase catalyzes the first step in the biosynthesis of coenzyme A, the major acyl group carrier in biology. In bacteria, regulation of pantothenate kinase activity is a major factor in controlling intracellular coenzyme A levels, and pantothenate analogs are growth-inhibiting antimetabolites. We have extended the structural information on Escherichia coli pantothenate kinase by determining the structure of the enzyme.ADP. pantothenate ternary complex. Pantothenate binding induces a significant conformational change in amino acids 243-263, which form a "lid" that folds over the open pantothenate binding groove. The positioning of the substrates suggests the reaction proceeds by a concerted mechanism that involves a dissociative transition state, although the negative charge neutralization of the gamma-phosphate by Arg-243, Lys-101, and Mg(2+) coupled with hydrogen bonding of the C1 of pantothenate to Asp-127 suggests different interpretations of the phosphoryl transfer mechanism of pantothenate kinase. N-alkylpantothenamides are substrates for pantothenate kinase. Modeling these antimetabolites into the pantothenate active site predicts that they bind in the same orientation as pantothenate with their alkyl chains interacting with the hydrophobic dome over the pantothenate pocket, which is also accessed by the beta-mercaptoethylamine moiety of the allosteric regulator, coenzyme A. These structural/biochemical studies illustrate the intimate relationship between the substrate, allosteric regulator, and antimetabolite binding sites on pantothenate kinase and provide a framework for studies of its catalysis and feedback regulation. | Ottenhof HH, Ashurst JL, Whitney HM, Saldanha SA, Schmitzberger F, Gweon HS, Blundell TL, Abell C, Smith AG (2004)
Organisation of the pantothenate (vitamin B5) biosynthesis pathway in higher plants.
The Plant journal : for cell and molecular biology 37, 61-72 [PubMed:14675432]
[show Abstract]
Pantothenate (vitamin B5) is the precursor for the biosynthesis of the phosphopantetheine moiety of coenzyme A and acyl carrier protein, and is synthesised in Escherichia coli by four enzymic reactions. Ketopantoate hydroxymethyltransferase (KPHMT) and pantothenate synthetase (PtS) catalyse the first and last steps, respectively. Two genes encoding KPHMT and one for PtS were identified in the Arabidopsis thaliana genome, and cDNAs for all three genes were amplified by PCR. The cDNAs were able to complement their respective E. coli auxotrophs, demonstrating that they encoded functional enzymes. Subcellular localisation of the proteins was investigated using green fluorescent protein (GFP) fusions and confocal microscopy. The two KPHMT-GFP fusion proteins were targeted exclusively to mitochondria, whereas PtS-GFP was found in the cytosol. This implies that there must be transporters for pathway intermediates. KPHMT enzyme activity could be measured in purified mitochondria from both pea leaves and Arabidopsis suspension cultures. We investigated whether Arabidopsis encoded homologues of the remaining two pantothenate biosynthesis enzymes from E. coli, l-aspartate-alpha-decarboxylase (ADC) and ketopantoate reductase (KPR). No homologue of ADC could be identified using either conventional blast or searches with the program fugue in which the structure of the E. coli ADC was compared to all the annotated proteins in Arabidopsis. ADC also appears to be absent from the genome of the yeast, Saccharomyces cerevisiae, by the same criteria. In contrast, a putative Arabidopsis oxidoreductase with some similarity to KPR was identified with fugue. | Youssef J, Davis A, Roberts LJ, Swift LL, Morrow JD, Badr M (2002)
Pantothenic acid: an organ-specific pro-oxidant vitamin. Brain and liver neuroprostane levels in rats fed a pantothenic acid-deficient diet.
Advances in experimental medicine and biology 507, 551-555 [PubMed:12664639] | Said HM, Kumar C (1999)
Intestinal absorption of vitamins.
Current opinion in gastroenterology 15, 172-176 [PubMed:17023940]
[show Abstract]
This article provides an overview of advances in understanding the cellular and molecular mechanisms and regulation of intestinal absorption processes of vitamins. The vitamins covered are the water-soluble vitamins folic acid, cobalamin (vitamin B12), biotin, pantothenic acid, and thiamine (vitamin B1) and the lipid-soluble vitamin A. For folate, significant advances have been made in regard to i) digestion of dietary folate polyglutamates to folate monoglutamates by the cloning of the responsible enzyme; ii) identification of the cDNA responsible for the intestinal folate transporter; iii) delineation of intracellular mechanisms that regulate small intestinal folate uptake; and iv) identification and characterization of a specific, pH-dependent, carrier-mediated system for folate uptake at the luminal (apical) membrane of human colonocytes. Studies on cobalamine have focused on cellular and molecular characterization of the intrinsic factor and its receptor. Studies on biotin transport in the small intestine have shown that the uptake process is shared by another water-soluble vitamin, pantothenic acid. Furthermore, a Na-dependent, carrier-mediated biotin uptake system that is also shared with pantothenic acid has been identified at the apical membrane of human colonocytes. This carrier is believed to be responsible for the absorption of the bacterially synthesized biotin and pantothenic acid in the large intestine. Also, preliminary studies have reported the cloning of a biotin transporter from the small intestine. As for thiamine intestinal transport, a study has shown thiamine uptake by small intestinal biopsy specimens to be via a carrier-mediated, Na-independent mechanism, which appears to be up-regulated in thiamine deficiency. Studies on vitamin A intestinal absorption have shown the existence of a receptor-mediated mechanism for the uptake of retinol bound to retinol-binding protein in the small intestine of suckling rats. Another study has shown that retinoic acid increases the mRNA level of the cellular retinol binding protein II and the rate of retinol uptake by Caco-2 intestinal epithelial cells. The study suggested that retinoids may play a role in the regulation of vitamin A intestinal absorption. | Salehi E (1969)
[Administration of pantothenic acid as a curare antidote].
Die Medizinische Welt 37, 2038-2040 [PubMed:5352084] | PELTON RB, WILLIAMS RJ (1958)
Effect of pantothenic acid on the longevity of mice.
Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 99, 632-633 [PubMed:13614445] |
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