Pantothenic Acid Derivatives Research Articles

Comparative Study of the Healing Process of Disbudding Wounds in Calves Using Bepanthene® or an Antibiotic Spray.

The process of disbudding female calves is a common procedure in many dairy farms, avoiding injuries caused by horns and reducing feed bunk space requirements. The most common method for disbudding calves is by the use of a cautery iron, responsible for destroying the horn-generating tissue. After the procedure, wounds may be treated with an antibiotic-based spray. Nowadays, antimicrobial resistance is a worldwide concern in both human and veterinary medicine, highlighting the need to invest in the monitoring of antimicrobial use and in the development of alternative treatments in favour of One Health. The goal of this study is to promote a reduction in the use of antibiotics in farm animals by investigating an alternative treatment for disbudding wounds. Bepanthene® (dexpanthenol, a derivative of pantothenic acid, a component of the B vitamin complex) is a plausible option, since it is widely used in human medicine for the treatment of skin irritations and burns. The comparison of the healing process of disbudding wounds treated with Bepanthene® or a chlortetracycline-based spray was achieved through the presentation of a randomly-ordered sequence of images of the lesions to a panel of convenience-selected and blinded-to-treatment evaluators, composed of seven veterinarian practitioners, five veterinary medicine students, and five human medical field nurses. In order to classify the lesions, the panel applied an adapted format of a validated healing scale (Bates-Jensen Wound Assessment Tool), incorporating seven parameters of evaluation, culminating in the values used for statistical analyses. In the practitioners' evaluation, a statistically significant effect for the factors of time and treatment in favour of Bepanthene® was found for the parameters "Edges", "Necrotic Tissue Type", and "Skin Colour Surrounding Wound", indicating that Bepanthene® is superior to the spray when considering these parameters of healing. The assessment by the veterinary students showed a significant effect for the factors of time and treatment for the parameters "Necrotic Tissue Type", in favour of the Bepanthene®, and "Granulation Tissue", in favour of the antibiotic spray, demonstrating no clear benefit for either treatment. Lastly, the evaluation performed by nurses showed a significant effect for the factors of time and treatment, in favour of the Bepanthene®, for the parameters "Necrotic Tissue Type" and "Skin Colour Surrounding Wound", leading to the conclusion that Bepanthene® is associated with better and faster healing when compared to the spray. Overall, these findings lead us to suggest that Bepanthene® presents a better healing index compared to a chlortetracycline-based spray, allowing it to be safely used as a substitute to an antimicrobial agent.

Rationale for the use of dexpanthenol drugs as part of the external therapy of dermatoses in children and adults

Impaired skin barrier plays a major role in the development of many skin diseases and conditions such as dry skin, sensitive skin, atopic dermatitis, contact dermatitis, etc. The topical therapy aims at not only suppressing the inflammatory response in the skin, but also at regenerating the destroyed protective epidermal lipid barrier in atopic dermatitis patients. Dexpanthenol was produced by synthesis in the middle of the last century and is a derivative of pantothenic acid. Topical dexpanthenol is well absorbed through the skin, where it is converted into pantothenic acid, a component of coenzyme A, and thus participates in the regulation of the synthesis of fatty acids and sphingolipids, components of the stratum corneum. Therefore, pantothenic acid is essential for the normal functioning of the epithelium. Topical dexpanthenol improves skin hydration due to its hygroscopic properties and ability to retain moisture. The hydrating effect is interrelated with its capacity to regenerate the epidermal barrier of the skin. Dexpanthenol also enhances the differentiation of corneocytes and lipid synthesis, stimulating the regeneration of the epidermis. Numerous studies show that the efficacy of dexpanthenol is comparable to the efficacy of glucocorticosteroids by a weak degree of activity. Dexpanthenol is the active ingredient of Pantoderm, which is available as cream and ointment. Pantoderm ointment and cream contain 5% dexpanthenol. The article presents its own clinical reports of the treatment of patients with atopic dermatitis and administration of the combination therapy. It may be concluded that the use of topical glucocorticosteroids combined with dexpanthenol can increase the effectiveness of therapy in patients with atopic dermatitis.

Pantothenic Acid Uptake and Metabolism by Red Blood Cells of Rats

Red blood cells (RBC) of rats and humans contain pantothenic acid (PA) derivatives, generally referred to as bound PA, which were never characterized or quantitated. This study was undertaken to define those factors that determine the rates of uptake and efflux of PA, and possibly PA derivatives, in RBC. Uptake of PA by RBC was studied by incubating RBC with different concentrations of PA (0.34–34.0 µmol/L), each containing [14C]PA (0.34 µmol/L) at 37°C for 3–360 min. The effects of Na+, energy and pH on the uptake of PA in RBC were determined in experiments varying media concentrations of Na+ (0–152 mmol/L), glucose (0 and 10 mmol/L) or pH (7.2–7.6). The release of PA from RBC was studied by incubating RBC containing [14C]PA (0.10–10.4 nmol/107 RBC, final concentration) in fresh media at 37°C for 10–240 min. Uptake and efflux of PA were found to be nonsaturable; uptake was not affected by Na+, energy or pH. Quantitative and qualitative determination of PA derivatives was by enzymatic hydrolysis of lysed RBC, followed by analysis of PA by RIA and paper chromatography. The RBC were found to contain PA, 4′-phosphopantothenic acid and pantetheine. We conclude that PA diffuses passively into and out of RBC and that RBC contain only PA, 4′-phosphopantothenic acid, pantetheine and no CoA.

Effects of Panthenol and N-Acetylcysteine on Changes in the Redox State of Brain Mitochondria under Oxidative Stress In Vitro.

The glutathione system in the mitochondria of the brain plays an important role in maintaining the redox balance and thiol–disulfide homeostasis, whose violations are the important component of the biochemical shifts in neurodegenerative diseases. Mitochondrial dysfunction is known to be accompanied by the activation of free radical processes, changes in energy metabolism, and is involved in the induction of apoptotic signals. The formation of disulfide bonds is a leading factor in the folding and maintenance of the three-dimensional conformation of many specific proteins that selectively accumulate in brain structures during neurodegenerative pathology. In this study, we estimated brain mitochondria redox status and functioning during induction of oxidative damage in vitro. We have shown that the development of oxidative stress in vitro is accompanied by inhibition of energy metabolism in the brain mitochondria, a shift in the redox potential of the glutathione system to the oxidized side, and activation of S-glutathionylation of proteins. Moreover, we studied the effects of pantothenic acid derivatives—precursors of coenzyme A (CoA), primarily D-panthenol, that exhibit high neuroprotective activity in experimental models of neurodegeneration. Panthenol contributes to the significant restoration of the activity of enzymes of mitochondrial energy metabolism, normalization of the redox potential of the glutathione system, and a decrease in the level of S-glutathionylated proteins in brain mitochondria. The addition of succinate and glutathione precursor N-acetylcysteine enhances the protective effects of the drug.

Energy metabolism and redox status of the glutathione system in experimental brain ischemia and its correction by metabolic neuroprotectors

The changes in the parameters of oxidative stress, energy metabolism, and redox potential of the glutathione system in the rat brain following cerebral ischemia were studied. To correct metabolic disorders, the pantothenic acid derivatives were used in combination with precursors of glutathione biosynthesis and selenium substances.Cerebral ischemia was modeled by ligating the both common carotid arteries in rats for 2 h. Drugs were administered i.p. in the following doses: panthenol – 400 mg/kg, N-acetylcysteine – 150, nanoselen – 1 mg/kg, three times: 1 h before ligation of the carotid arteries, at the time of ligation and 1 hour after ligation. We showed that the development of oxidative stress caused by ischemia is accompanied by the changes in the parameters of energy metabolism and the pentose phosphate pathway in the cerebral hemispheres. Simultaneously, there are a decrease in the GSH level, an increase in the GSSG content, a decrease in the GSH/GSSG ratio, and the activation of enzymes of redox transformations of glutathione.The redox potential of the glutathione system decreases and shifts towards oxidation, while the level of S-glutathionylated proteins increases. Thus, the value of the GSH/GSSG ratio and the protein glutathionylation intensity are the sensitive indicators of the redox potential in the brain tissue and can be used as markers of the extent of changes in the redox balance. The panthenol injection to animals leads to a decrease in the content of free radical oxidation products, violations of oxidative phosphorylation and restoration of thiol-disulfide balance in the brain. When panthenol is administered together with N-acetylcysteine and nanoselen, the corrective effect of panthenol is enhanced.

Modulating Oxidative Stress Indices and Thiol-Disulfide Balance in the Brain Structures by Pantothenic Acid Derivatives in an Experimental Model of Parkinson’s Disease

Abstract—We studied changes in the indices of free-radical oxidation and thiol-disulfide status in the brain structures in the experimental model of Parkinson’s disease (PD) induced by administration of rotenone to rats. Pantothenic acid derivatives, such as panthenol (PL), pantethine (PT), and homopantothenic acid (HPA) were used as neuromodulators. It was found that redox imbalance in the brain induced by rotenone is accompanied by the activation of free-radical processes, pronounced inhibition of antioxidant defense, a considerable decrease in the glutathione system reduction potential, and increased protein glutathionylation. The strongest changes were in the basal ganglia of the brain. PL and PT but not HPA, decrease the changes in the free-radical oxidation and thiol-disulfide balance in the brain structures. During experimental neurotoxicosis, the mechanisms of neuroprotective action of PL and PT, which are linked with the changes in the biosynthesis of CoA, are, obviously, related to their ability to increase the reduction potential of the glutathione system, thus mitigating the effects of oxidative stress.

S-glutathionylation of proteins in various types of neurodegenerative pathology and protective effects of pantothenic acid derivatives

@page { size: 21.59cm 27.94cm; margin: 2cm } p { margin-bottom: 0.25cm; direction: ltr; color: #000000; line-height: 115%; orphans: 2; widows: 2; background: transparent } p.western { font-family: Liberation Serif, Times New Roman, serif; font-size: 12pt; so-language: en-US } p.cjk { font-family: DejaVu Sans; font-size: 12pt; so-language: zh-CN } p.ctl { font-family: FreeSans, Times New Roman; font-size: 12pt; so-language: hi-IN } a:link { color: #000080; text-decoration: underline } a.western:link { so-language: zxx } a.ctl:link { so-language: zxx } We studied changes in S-glutathionylated proteins (PSSG) content in rat brain structures in different experimental models of neurodegenerative pathology, as well as the possibility of correcting these changes with pantothenic acid derivatives. We have shown that the content of PSSG significantly increases in brain structures in all the models of neurotoxicosis that we studied, and this increase is observed to the greatest extent precisely in those structures where a particular neurotoxin has the most pronounced effect. Thus, the content of PSSG is a sensitive marker of post-translational protein modification. Precursors of CoA reduce S-glutathionylation of proteins, since HPA, which is not a precursor of CoA, does not have a protective effect in relation to PSSG.

The effect of intraurethral dexpanthenol in hypospadias repair: experimental rabbit study

In this study, the authors aimed to research the histopathologic effects of intraurethral use of dexpanthenol for hypospadias repair. Dexpanthenol is a derivative of pantothenic acid, a B complex vitamin. Pantothenic acid is a molecule contributing in the structure of coenzyme A. It decreases the release of myeloperoxidase from granulocytes and inhibits the formation of free oxygen radicals, and it exhibits an anti-inflammatory effect by increasing mitotic activity. The objective of this study is to evaluate the use of dexpanthenol after a tubularized incised plate urethroplasty (TIP) on wound healing, inflammation, and fibrosis. In this study, 18 healthy male New Zealand white rabbits weighing 2500-3000g were used. The 18 rabbits were randomly divided into 3 groups. For the hypospadias model, rabbits had a urethral catheter inserted in the urethra and a ventral midline incision was made from the glans tip to the central line of the penis. Afterward, the incision was closed with Vicryl (7/0) using the continuous suture technique, and urethroplasty was completed. For fourteen days, group I had 0.9% saline solution administered intraurethrally twice per day with a 22G catheter sleeve (control group), group II had one dose of 500mg/kg dexpanthenol (Bepanthene®; Bayer Turk Chemical Industry Limited Company, Turkey) ampoule and one dose of saline solution administered in the same way, and group III had two doses of 500mg/kg dexpanthenol ampoule administered. On the fifteenth day, the penis was degloved and rabbits had penectomy performed with samples sent to the pathology department for histopathological assessment. The degree of fibrosis and inflammation in group I (control group) was more severe than groups II and III. The differences between groups I and II were statistically significantly different for both fibrosis and inflammation (P=0.018 and P=0.041, respectively). The differences between groups I and III were also statistically significantly different for both fibrosis and inflammation (P=0.019 and P=0.011, respectively). Groups II and III were not different significantly for fibrosis and inflammation (P>0.05). This study shows that intraurethral dexpanthenol application has positive effects on fibrosis and inflammation. The main limitations of the study are that the hypospadias model was created surgically and long-term follow-up for fistula formation was not assessed. Administration of intraurethral dexpanthenol after hypospadias repair has positive effects on fibrosis and inflammation.

Noncovalent Modification of Nanodiamonds with Tritium-Labeled Pantothenic Acid Derivatives

The efficiency of tritium labeling of salts of pantothenic (HO–R–COOH), hopantenic (HO–R–CH2–COOH), and 4-D-phosphopantothenic [(HO)2P(=O)–O–R–COOH] acids [R = CH2C(CH3)2CHOH–CONH(CH2)2] with thermal activation of tritium at target temperatures of 77 and 295 K was studied. The phosphate group inhibits the isotope exchange. The tritium-labeled compounds were used for studying the adsorption of pantothenic acid derivatives from aqueous solutions and in the presence of 0.9% NaCl at 297 ± 3 K onto nanodiamonds prepared by detonation synthesis (NDs). Preparation of stable ND suspensions in advance enhances the ability of NDs to adsorb the compounds studied. The parameters of the equation describing the sorption isotherms at different ionic strengths of the solution were calculated. The strength of the adsorbate retention in contact with water, 0.9% NaCl solution, 0.01 M HCl solution, and 40 g L−1 bovine serum albumin (BSA) solution was determined. The data obtained allow two mechanisms of the adsorbate retention on the ND surface to be considered: reversible adsorption due to ionic interactions and irreversible binding due to hydrophobic interactions. The strongly bound molecules undergo slow desorption in the presence of BSA. The revealed trends confirm high potential of NDs as a drug delivery platform.

Ethyl 2,4-dicarboethoxy pantothenate, a derivative of pantothenic acid, prevents cellular damage initiated by environmental pollutants through Nrf2 activation

BackgroundRecently, environmental pollutants have become a concern not only for respiratory organs but also for skin-related human health, because skin is localized at the border between the human body and the external environment and is easily influenced by environmental pollutants. ObjectiveHere, we investigated the effects of a novel pantothenic acid (PA) derivative, ethyl 2,4-dicarboethoxy pantothenate (EDCEP), on a diesel particulate extract (DPE) as a representative environmental pollutant that generates reactive oxygen species (ROS) through the activation of aryl hydrocarbon receptor (AHR) signaling. MethodsWe characterized the effects of PA and EDCEP on normal human epidermal keratinocytes (NHEKs) exposed to DPE or H2O2 as a general oxidative stress stimulator. Cell viability and intracellular ROS levels were evaluated using the 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyltetrazolium bromide (MTT) assay and the 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) assay, respectively. Further, we investigated the substantial effects and the underlying mechanism of EDCEP, which elicited a reduction of intracellular ROS. ResultsPA and EDCEP restored the decreases of cell viability induced by DPE and also repressed the up-regulation of CYP1A1 mRNA expression induced by DPE. Interestingly, the effects of PA and EDCEP on intracellular ROS levels showed different responses. EDCEP reduced intracellular ROS levels stimulated by DPE or by exposure to H2O2. EDCEP suppressed the secretion of tumor necrosis factor (TNF-α) and reduced the level carbonylated proteins in reconstructed human epidermal equivalents topically treated with DPE. EDCEP up-regulated the mRNA expression levels of nuclear factor E2-related factor 2 (Nrf2), γ-glutamyl cysteine synthase (γ-GCS), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) and in addition, increased intracellular glutathione (GSH) levels. ConclusionEDCEP reduces cellular damage initiated by environmental pollutants by stimulating the intracellular defense system against ROS through the activation of Nrf2, and by interfering with AHR signaling pathway activation.

Combined treatment with pantothenic acid derivatives and memantine alleviates scopolamine-induced amnesia in rats: The involvement of the thiol redox state and coenzyme A

Free-radical-mediated processes are involved in a variety of physiological events, while oxidative stress and related redox deregulation are implicated in various pathological events. Tripeptide glutathione plays an important role in the antioxidant defense of the brain, particularly in the maintenance of the optimal redox state in neurons and glial cells. We studied the combined effects of pantothenic acid derivatives, pantothenol and calcium pantothenate, and memantine, which is a glutamate receptor antagonist that is widely used for the treatment of dementia, on amnesia induced by scopolamine in rats. Scopolamine induced amnesia in rats; however, unexpectedly, this effect was even more expressed in the memantine-pretreated animals. Memory impairments were less manifested in the rats that were pretreated with memantine in combination with panthenol or calcium pantothenate. The detrimental scopolamine effect on memory was accompanied by significant depletions of glutathione and coenzyme A in the brain. While memantine recovered the glutathione status to some extent, it nevertheless further aggravated the scopolamine influence on coenzyme A levels. An alleviation of scopolamine-induced memory impairments that was observed after combined pretreatment with memantine and panthenol or calcium pantothenate was accompanied by a normalization of coenzyme A levels, while the effects on glutathione redox did not correlate with the behavioral data.

High Specificity in Response of the Sodium-Dependent Multivitamin Transporter to Derivatives of Pantothenic Acid

Essential nutrients are attractive targets for the transport of biologically active agents across cell membranes, since many are substrates for active cellular importation pathways. The sodium-dependent multivitamin transporter (SMVT) is among the best characterized of these, and biotin derivatives have been its most popular targets. We have surveyed 45 derivatives of pantothenic acid, another substrate of SMVT, long known as a competitive inhibitor of biotin transport. Variations of the β-alanyl fragment of pantothenate were uniformly rejected by the transporter, including derivatives with very similar steric and acidic characteristics to the natural substrate. The secondary hydroxyl of the 2,2-dimethyl-1,3-propanediol (pantoyl) fragment was the only position at which potential linkers could be attached while retaining activity as an inhibitor of biotin uptake and a substrate for sodium-dependent transport. However, triazole conjugates to several drug-like cargo motifs were not accepted as substrates by human SMVT in cell culture. Two compounds were observed which did not inhibit biotin uptake but were themselves transported in a sodium-dependent fashion, suggesting more complex behavior than expected. These studies represent the most extensive examination to date of pantothenate as an anchor for SMVT-mediated drug delivery, showing that this route requires further investigation before being judged promising.

The effects of derivatives of pantothenic acid on free-radical processes and the corticosterone level in the hippocampus and neocortex of rats after interoceptive stress

In this study, the effects of interoceptive stress on the indices of free-radical oxidation and the corticosterone contents in the brain and blood of male rats were examined. In addition, we studied the effects of the GABA-like nootropic drug calcium hopanthenate and panthenol on these indices after stress. Interoceptive stress was induced by intraperitoneal injection of bacterial lipopolysaccharide and the studies were performed 24 h after injection. The derivatives of pantothenic acid substantially attenuated corticosterone accumulation in the hippocampus after interoceptive stress induced by systemic immune challenge but did not prevent a stress-induced increase in the level of substances that reacted with thiobarbituric acid in the blood of the animals.

Increase in the specific radioactivity of tritium-labeled compounds obtained by tritium thermal activation method

Abstract A method of tritium introduction into different types of organic molecules that is based on the interaction of atomic tritium with solid organic target is described. Tritium atoms are formed on the hot W-wire, which is heated by the electric current. Such an approach is called “tritium thermal activation method”. Here we summarize the results of labeling globular proteins (lysozyme, human and bovine serum albumins); derivatives of pantothenic acid and amino acids; ionic surfactants (sodium dodecylsulfate and alkyltrimethylammonium bromides) and nonionic high-molecular weight surfactants – pluronics. For the first time it is observed that if the target-compound is fixed and its radicals are stable the specific radioactivity of the labeled product can be drastically increased (up to 400 times) when the target temperature is ca. 295 K compared with the results obtained at 77 K. The influence of labeling parameters as tritium gas pressure, exposure time and W-wire temperature was tested for each target temperature that results in the optimum labeling conditions with high specific radioactivity and chemical yield of the resulting compound.

Geminal dialkyl derivatives of N-substituted pantothenamides: Synthesis and antibacterial activity

As a key precursor of coenzyme A (CoA) biosynthesis, pantothenic acid has proven to be a useful backbone to elaborate probes of this biosynthetic pathway, study CoA-utilizing systems, and design molecules with antimicrobial activity. The increasing prevalence of bacterial strains resistant to one or more antibiotics has prompted a renewed interest for molecules with a novel mode of antibacterial action such as N-substituted pantothenamides. Although numerous derivatives have been reported, most are varied at the terminal N-substituent, and fewer at the β-alanine moiety. Modifications at the pantoyl portion are limited to the addition of an ω-methyl group. We report a synthetic route to N-substituted pantothenamides with various alkyl substituents replacing the geminal dimethyl groups. Our methodology is also applicable to the synthesis of pantothenic acid, pantetheine and CoA derivatives. Here a small library of new N-substituted pantothenamides was synthesized. Most of these compounds display antibacterial activity against sensitive and resistant Staphylococcus aureus. Interestingly, replacement of the ProR methyl with an allyl group yielded a new N-substituted pantothenamide which is amongst the most potent reported so far.

The Effect of Pantothenic Acid Deficiency on Keratinocyte Proliferation and the Synthesis of Keratinocyte Growth Factor and Collagen in Fibroblasts

It has been reported that pantothenic acid (vitamin B5) and panthenol, an alcohol derivative of pantothenic acid, have beneficial moisturizing effects on the skin. However, few studies have investigated the mechanism of action of pantothenic acid on skin tissues. We tried to clarify the role of pantothenic acid on skin function by using keratinocytes and fibroblasts. The depletion of pantothenic acid from the culture medium suppressed keratinocyte proliferation and promoted differentiation. Moreover, pantothenic acid depletion decreased the synthesis of keratinocyte growth factor and procollagen 4a2 in fibroblasts. These results suggest that pantothenic acid is essential for maintaining keratinocyte proliferation and differentiation.

The Effect of Dexpanthenol in Postoperative Patients

Purpose: The purpose of this study was to compare the efficacy of dexpanthenol in postoperative patients. Dexpanthenol, the alcohol derivative of pantothenic acid, is believed to be a precursor of acetylcholine through its incorporation into coenzyme-A. Methods: From June 2005 to December 2005, 130 curative abdominal surgery, which were divided into a dexpanthenol group with 65 patients and a control group with 65 patients, were prospectively and randomly studied for recovery of bowel motility. Results: No significant difference was found between the two groups as to incidence of postoperative ileus (16.9% vs. 15.4%, P=0.081), the time to flatus (77.2±38.4 vs. 77.9±31.9 hours, P=0.90), the time to defecation (5.3±2.7 vs. 5.1±2.6 days, P=0.77), the time to resumption of meals (7.9±4.0 vs. 8.9±4.2 days, P=0.17), and the duration of hospital stay (16.4±7.8 vs. 17.9±11.5 days, P=0.39). Conclusions: Since no differences in the postoperative bowel motility were observed between the two groups, dexpanthenol is not recommended for general surgical use.

Syntheses of Pantolactone and Pantothenic Acid Derivatives as Potential Lipid Regulating Agents

A series of pantolactone and pantothenic acid derivatives (1–10) were synthesized to be tested for their potential as lipid regulating agents that act as Coenzyme‐A mimics. The syntheses were performed with moderate to high yields.

Pantothenic acid and pantothenol increase biosynthesis of glutathione by boosting cell energetics

We have previously observed (summarized in BioFactors 17 (2003) 61) that pantothenic acid, pantothenol and other derivatives that are precursors of CoA protect cells and whole organs against peroxidative damage by increasing the content of cell glutathione. The present investigation was aimed to elucidate the mechanism of this increase in human lymphoblastoic (Jurkat) cells. It showed that incubation of the cells with pantothenic acid or pantothenol increased mainly the content of free glutathione, with little effect on protein-bound glutathione. Buthionine sulfoximine, an inhibitor of glutathione synthesis, prevented this increase. Increase of the content of free glutathione, as produced by pantothenic acid or pantothenol, was largely prevented by respiratory chain inhibitor rotenone, inhibitor of mitochondrial ATP synthesis oligomycin and uncoupler of oxidative phosphorylation of carbonyl cyanide 3-chlorophenylhydrazone. These treatments also decreased the cellular content of ATP. Preincubation with pantothenic acid or pantothenol also increased cell respiration with pyruvate as the exogenous substrate. Although no significant increase of total cell CoA content could be found, it is concluded that the increase of the glutathione level was due to increased production of ATP that was, in turn, a result of the increased content of mitochondrial CoA.

One-pot chemoenzymatic preparation of coenzyme A analogues

A rapid and stoichiometric method for the synthesis of analogues of coenzyme A is described. The method links the enzymes pantothenate kinase, phosphopantotheine adenylyltransferase, and dephosphocoenzyme A kinase in vitro to generate a variety of CoA analogues from chemically synthesized pantothenic acid derivatives. The Escherichia coli CoA biosynthetic enzymes were overexpressed as hexa-histidine-tagged proteins, providing an abundant source of pure active catalysts for the reaction. The synthesis of five novel CoA derivatives is reported and the method is shown to be robust and tolerant of a number of different pantothenic acid structures, which indicates that the procedure should be widely applicable.