Pantothenic Acid Supplementation Research Articles

A novel SLC5A6 homozygous variant in a family with multivitamin-dependent neurometabolic disorder: Phenotype expansion and long-term follow-up

The sodium-dependent multivitamin transporter (hSMVT) encoded by the SLC5A6 gene is required for the intestinal absorption of biotin, pantothenic acid and lipoate, three micronutrients essential for normal growth and development. Systemic deficiency of these elements, either occurring from nutritional causes or genetic defects, is associated with neurological disorders, growth delay, skin and hair changes, metabolic and immunological abnormalities. A few patients with biallelic variants of SLC5A6 have been reported, exhibiting a spectrum of neurological and systemic clinical features with variable severity. We describe three patients from a single family carrying a homozygous p.(Leu566Valfs*33) variant of SLC5A6 disrupting the frame of the C-terminal portion of the hSMVT. In these patients, we documented a severe disorder featuring developmental delay, sensory polyneuropathy, optic atrophy, recurrent infections, and repeated episodes of intestinal pseudo-obstruction. Two patients who did not receive multivitamin supplementation therapy died in early infancy. In a third patient, early supplementation of biotin and pantothenic acid stabilized the clinical picture changing the course of the disease. These findings extend genotype-phenotype correlations and show how a timely and lifelong multivitamin treatment may be crucial to reduce the risk of life-threatening events in patients with pathogenic variants of the SLC5A6 gene.

Effects of dietary pantothenic acid on growth, antioxidant ability and innate immune response in juvenile black carp

An 8-week feeding study was conducted to examine how dietary pantothenic acid (PA) affects growth, antioxidant ability and innate immunity in juvenile black carp (Mylopharyngodon piceus). Juvenile fish (7.35 ± 0.06 g) were fed diets with PA at 0, 5, 10, 20, 40 and 80 mg/kg, respectively. The highest weight gain (WG), specific growth rate (SGR) and protein efficiency ratio (PER) were obtained with 10 mg/kg dietary PA (p < 0.05), as well as the lowest feed conversion ratio (FCR). Adequate dietary PA (10 and 20 mg/kg) markedly upregulated neuropeptide Y (NPY), orexin (ORX) and ghrelin (GRL) and downregulated cholecystokinin (CCK) in the brain of these animals (p < 0.05). Intestinal sodium-dependent multivitamin transporter (SMVT) expression and α amylase, trypsin, chymotrypsin and lipase activities were all improved after supplementation of PA at 10 or 20 mg/kg (p < 0.05). In addition, adequate dietary PA (10 and 20 mg/kg) significantly increased the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR), as well as the amounts of reduced glutathione (GSH) and total antioxidant capacity (T-AOC) in the liver of these animals (p < 0.05). Meanwhile, liver glutathione S-transferase (GST) activity and malondialdehyde (MDA) amounts levels were both markedly decreased with dietary PA at 10 or 20 mg/kg (p < 0.05). Furthermore, adequate dietary PA significantly elevated the mRNA amounts of NFE2-related nuclear factor 2 (Nrf2) and downregulated Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b (p < 0.05), and remarkably upregulated innate defense molecules, including lysozyme (LYZ), natural resistance-associated macrophage protein (NRAMP), liver-expressed antimicrobial peptide 2 (LEAP-2), hepcidin (HEPC), complement 3 (C3) and complement 9 (C9) in the liver (p < 0.05). Meanwhile, elevated dietary PA resulted in increased LYZ activity and C3 content and decreased aspartate aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum samples from juvenile black carp compared with the groups fed PA-deficient diets (p < 0.05). Moreover, 10, 20 and 40 mg/kg PA-containing diets starkly downregulated intestinal interleukin 8 (IL-8) and IL-11 at the mRNA level in comparison with the PA-deficient diet (0 mg/kg) (p < 0.05). However, PA supplementation at 10, 20 or 40 mg/kg resulted in increased intestinal zonula occludens-1 (ZO-1), ZO-2, ZO-3, claudin 3, claudin 4, claudin 8, claudin 15 and occludin mRNA levels in M. piceus in comparison with the 0 mg/kg PA group (p < 0.05). Jointly, the above findings suggested adequate dietary PA (10 and 20 mg/kg) enhances feed utilization and growth performance, as well as antioxidant capacities and non-specific immune reactions in juvenile M. piceus.

Effects of Pantothenic Acid on Growth Performance, Oxidative Stress, and Lipid Content in High-Fat-Fed Megalobrama amblycephala

This study was to elucidate the effects of dietary pantothenic acid (PA) on growth, lipid metabolism, and antioxidant status in juvenile blunt snout bream Megalobrama amblycephala. Fish were fed with four experimental diets containing two lipid levels (5% and 11%) and two PA supplementation levels (24 mg kg-1 and 240 mg kg-1) for eight weeks. The results showed that diets containing 11% lipid significantly increased condition factor, mesenteric fat index, triacylglycerol (TG), and cholesterol (TCH) in the liver as well as total lipid content and TCH in the muscle ( P &lt; 0.05 ), but significantly decreased specific growth rate and whole-body protein ( P &lt; 0.05 ). As the dietary lipid level increased, hepatic antioxidant enzyme activities were significantly increased ( P &lt; 0.05 ) as well as malondialdehyde content ( P &lt; 0.05 ). Besides, cytosolic cytochrome c concentration was also significantly ( P &lt; 0.05 ) increased, while mitochondrial protein, cytochrome c, and Na+-K+-ATPase activities were significantly decreased ( P &lt; 0.05 ). There were no significant changes on growth performance and body composition of PA supplementation. Then, significantly negative ( P &lt; 0.05 ) interactions were observed between dietary lipid and PA supplementation on EPA, DHA, and EPA + DHA content of the muscle. Saturated fatty acid (SFA) and polyunsaturated fatty acid (PUFA) contents in the liver were significantly increased ( P &lt; 0.05 ) with dietary lipid level increased, while liver monounsaturated fatty acid (MUFA) was significantly decreased ( P &lt; 0.05 ). Muscle SFA, DHA, and EPA + DHA contents were significantly decreased ( P &lt; 0.05 ) when dietary fat level increased. Meanwhile, EPA, DHA, and EPA + DHA content was significantly decreased ( P &lt; 0.05 ) with dietary high PA supplementation. On the whole, a high PA supplementation level of 240 mg kg-1 could alleviate lipid content accumulated and oxidative damage induced by a high-fat diet.

Effect of supplemental pantothenic acid on lipid metabolism and antioxidant function of Apis mellifera worker bees

This study was conducted to investigate the effects of pantothenic acid (PA) on the lipid metabolism, and antioxidant function of Apis mellifera workers. The results showed that ether extract (EE) content of bees’ body was significantly decreased when workers were supplemented with 147 mg/kg PA (P < 0.05). Further, supplemental PA reduced triglycerides (TG) and total cholesterol (TCHO) content in the hemolymph (P < 0.05), while 39.2 mg/kg PA supplementation improved hemolymph high-density lipoprotein cholesterol (HDL-c) concentration, while 261.6 mg/kg PA reduced low-density lipoprotein cholesterol (LDL-c) concentration (P < 0.05). C12:0, C14:1, and C18:0 content values were notably increased in PA-supplemented groups, while those of C14:0, C18:2n-6, C20:4n-6, polyunsaturated fatty acids (PUFA), and PUFA/saturated fatty acids were decreased (P < 0.05), while levels correlated with those of dietary PA. Malondialdehyde (MDA) content showed a downward trend in response to PA supplementation; however, total superoxide dismutase (T-SOD) was increased (P < 0.05). Furthermore, fatty acid synthase (FAS) mRNA levels were significantly downregulated in bees supplemented 9.8, 19.6, and 39.2 mg/kg (P < 0.05) and lipase activity significantly improved following supplementation with 39.2, 78.4, and 147 mg/kg PA (P < 0.05). Thus, dietary PA significantly influenced worker bee lipid metabolism, and improved antioxidant function.

Effects of Pantothenic Acid Supplementation on Growth Performance, Carcass Traits, Plasma Parameters of Starter White Pekin Ducks Fed a Corn-Soybean Meal Diet.

Simple SummaryThe yield of meat duck has increased over the past decade. Precise nutrition of ducks would contribute to improve growth performance and feed efficiency. As one of the important B-vitamins, pantothenic acid is essential for animals, and the deficiency of this vitamin could lead to growth depression, high mortality, and abnormal glucose metabolism. Similarly, pantothenic acid is also needed for ducks. The objectives of this study were to evaluate the effects of dietary pantothenic acid levels on growth performance, carcass traits, and plasma biochemical parameters of ducks, as well as the pantothenic acid requirement of ducks based on conventional corn–soybean meal diets. The results showed that among all ducks, the birds fed the basal diet without pantothenic acid supplementation had the lowest growth performance, breast meat yield, and plasma pantothenic acid and glucose contents. In addition, all these parameters increased linearly or quadratically as the dietary pantothenic acid level increased. The pantothenic acid requirements of starter male white Pekin ducks were 13.29–15.0 mg/kg. The data potentially provides theoretical support for the utilization of pantothenic acid in duck production.This study aimed to evaluate the effects of different dietary pantothenic acid levels on growth performance, carcass traits, and plasma biochemical parameters of starter Pekin ducks from 1 to 21 days of age, as well as the pantothenic acid requirement of starter ducks. A total of 384 one-day-old male white Pekin ducklings were assigned randomly into 6 dietary treatments, each with 8 replicate pens of 8 ducks. Ducks were fed conventional basal corn–soybean diets containing 8.5, 10.5, 12.5, 14.5, 16.5, and 18.5 mg/kg pantothenic acid for 21 days. Growth depression, poor pantothenic acid status, fasting hypoglycemia, and elevated plasma uric acid (UA) content were observed in the ducks fed the pantothenic acid-deficient basal diet (p < 0.05), and these adverse effects were ameliorated by pantothenic acid supplementation. Among all ducks, the birds fed the basal diet with no supplementation of pantothenic acid had the lowest body weight, average daily weight gain (ADG), average daily feed intake (ADFI), breast meat yield, and plasma pantothenic acid and glucose contents (p < 0.05), and the greatest plasma UA content (p < 0.05). In addition, all these parameters showed a linear or quadratic response as dietary pantothenic acid levels increased (p < 0.05). According to broken-line regression, the pantothenic acid requirements of starter male white Pekin ducks for body weight, ADG, and plasma pantothenic acid content were 13.36, 13.29, and 15.0 mg/kg, respectively. The data potentially provides theoretical support for the utilization of pantothenic acid in duck production.

Engineering acetyl-CoA supply and ERG9 repression to enhance mevalonate production in Saccharomyces cerevisiae.

Mevalonate is a key precursor in isoprenoid biosynthesis and a promising commodity chemical. Although mevalonate is a native metabolite in Saccharomyces cerevisiae, its production is challenged by the relatively low flux toward acetyl-CoA in this yeast. In this study we explore different approaches to increase acetyl-CoA supply in S. cerevisiae to boost mevalonate production. Stable integration of a feedback-insensitive acetyl-CoA synthetase (Se-acsL641P) from Salmonella enterica and the mevalonate pathway from Enterococcus faecalis results in the production of 1,390 ± 10 mg/l of mevalonate from glucose. While bifid shunt enzymes failed to improve titers in high-producing strains, inhibition of squalene synthase (ERG9) results in a significant enhancement. Finally, increasing coenzyme A (CoA) biosynthesis by overexpression of pantothenate kinase (CAB1) and pantothenate supplementation further increased production to 3,830 ± 120 mg/l. Using strains that combine these strategies in lab-scale bioreactors results in the production of 13.3 ± 0.5 g/l, which is ∼360-fold higher than previously reported mevalonate titers in yeast. This study demonstrates the feasibility of engineering S. cerevisiae for high-level mevalonate production.

Chronic pantothenic acid supplementation does not affect muscle coenzyme A content or cycling performance.

This study determined if supplementation with pantothenic acid (PA) for 16 weeks could increase skeletal muscle coenzyme A (CoASH) content and exercise performance. Trained male cyclists (n = 14) were matched into control or PA (6 g·day-1) groups. At 0, 4, 8, and 16 weeks, subjects performed an incremental time to exhaustion cycle with muscle biopsies taken prior to and following exercise. Prolonged PA supplementation did not change skeletal muscle CoASH and acetyl-CoA contents or exercise performance. Novelty: Supplementation with pantothenic acid for 16 weeks had no effect on skeletal muscle CoASH and acetyl-CoA content or exercise performance in trained male cyclists.

Pantothenic acid requirement of male White Pekin ducks from hatch to 21 days of age

An experiment was conducted to determine the effects of dietary pantothenic acid levels on growth performance, carcass traits, and pantothenic acid status of male White Pekin ducks from hatch to 21 days of age, and to evaluate the requirement of this B-vitamin for starter ducks. Different levels pantothenic acid (0, 2, 4, 6, 8, 10, and 20 mg/kg) were supplemented to corn-soy isolate protein basal diet to produce 7 dietary treatments with different analyzed total pantothenic acid levels (4.65, 6.80, 8.39, 9.98, 12.04, 13.70, and 22.50 mg/kg). A total of 448 one-day-old male White Pekin ducks were allotted to 7 dietary treatments with 8 replicate pens of 8 birds per pen. At 21 days of age, body weight, average daily weight gain (ADG), average daily feed intake (ADFI), gain to feed ratio (G/F), liver pantothenic acid content, as well as percentage yield of breast meat, leg meat, and abdominal fat were examined. The growth depression, exudate on eyelids, dermatosis, poor feathering, and 100 % of mortality were observed in the ducks fed the basal diet without pantothenic acid supplementation, and these adverse effects were ameliorated by pantothenic acid supplementation. The starter ducks on the diet containing 6.80 mg/kg of pantothenic acid had a lower parameter profile of body weight, ADG, ADFI, G/F, breast meat yield, abdominal fat yield, and liver pantothenic acid content compared to the birds fed the diets with higher levels of pantothenic acid (P < 0.05). And these criteria showed a linear or quadratic response to increasing dietary pantothenic acid levels (P < 0.05). The pantothenic acid requirements (based on dietary total pantothenic acid) of starter male White Pekin ducks for body weight, ADG, ADFI, G/F, and liver pantothenic acid content were 8.95, 8.95, 8.59, 9.56, and 10.22 mg/kg based on broken-line regression, while were 10.04, 10.05, 9.18, 11.01, and 11.24 mg/kg based on quadratic broken-line regression, respectively.

Effects of pantothenic acid on growth performance and antioxidant status of growing male white Pekin ducks

An experiment was conducted to investigate the effects of dietary pantothenic acid levels on growth performance, carcass traits, pantothenic acid status, and antioxidant status of male white Pekin ducks from 15 to 42 D of age and to evaluate the requirement of this vitamin for growing ducks. Different levels pantothenic acid (0, 2, 4, 6, 8, and 10 mg/kg) were supplemented to a corn-soy isolate protein basal diet to produce 6 dietary treatments with different analyzed total pantothenic acid levels (4.52, 6.44, 8.37, 9.88, 12.32, and 14.61 mg/kg). A total of 240 15-day-old male white Pekin ducks were allotted to 6 dietary treatments with 8 replicate pens of 5 birds per pen. At 42 D of age, growth performance, carcass traits, tissue pantothenic acid concentrations, and antioxidant status of white Pekin ducks were examined. Significant effects of dietary pantothenic acid on BW, average daily weight gain (ADG), plasma, and liver pantothenic acid concentrations were observed (P < 0.05) but not carcass traits. The growing ducks fed the basal diet without pantothenic acid supplementation had the lowest BW, ADG, plasma, and liver pantothenic acid content among all ducks (P < 0.05). In addition, the ducks fed the basal diet without pantothenic acid supplementation showed the lowest antioxidant capacity indicated by greatest plasma malondialdehyde content and lowest liver total antioxidant capacity (P < 0.05). And, these criteria responded linearly as dietary pantothenic acid levels increased (P < 0.05). These results indicated that dietary pantothenic acid supplementation improved growth performance and antioxidant status of the growing ducks. In accordance with the broken-line model, the pantothenic acid requirements (based on dietary total pantothenic acid) of male white Pekin ducks from 15 to 42 D of age for BW, ADG, and plasma and liver pantothenic acid contents were 10.18, 10.27, 12.06, and 10.79 mg/kg, respectively.

Effects of pantothenic acid and folic acid supplementation on total tract digestibility coefficient, ruminal fermentation, microbial enzyme activity, microflora and urinary purine derivatives in dairy bulls

AbstractThe effects of pantothenic acid (PA) and folic acid (FA) addition on digestibility coefficient, ruminal fermentation and urinary purine derivative (PD) excretion in dairy bulls were evaluated. Eight rumen-cannulated Holstein dairy bulls were allocated to a replicated 4 × 4 Latin square design according to a 2 × 2 factorial arrangement. Diets were supplemented with two levels of FA (0 or 8.0 mg/kg dietary dry matter [DM]) and two of PA (0 or 60 mg/kg DM). The PA × FA interaction was not significant for all variables. Both supplements increased DM intake and average daily gain, but decreased a feed conversion ratio. Digestibility of DM, organic matter, crude protein and neutral detergent fibre increased, but ether extract digestibility was unchanged for both supplements. Digestibility of acid detergent fibre only increased with FA supplementation. For both supplements, ruminal pH and ammonia nitrogen (N) decreased, but total volatile fatty acid (VFA) concentration increased. Acetate proportion only increased with FA supplementation. Propionate proportion decreased for both supplements. Consequently, the acetate to propionate ratio increased. For both supplements, activity of xylanase and pectinase, population of Ruminococcus albus, R. flavefaciens, Fibrobacter succinogenes and Ruminobacter amylophilus and total PD excretion increased. Additionally, activity of carboxymethylcellulase, cellobiase, α-amylase and protease, and population of total bacteria, fungi, protozoa, methanogens, Butyrivibrio fibrisolvens and Prevotella ruminicola increased with FA addition. The results suggested that PA and FA supplementation stimulated ruminal microbial growth and enzyme activity, resulting in an increased digestibility coefficient and ruminal total VFA concentration in dairy bulls.

Precision medicine in pantothenate kinase-associated neurodegeneration

Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas, mainly the basal ganglia. The predominant clinical symptoms include spasticity, progressive dystonia, Parkinson’s disease-like symptoms, neuropsychiatric alterations, and retinal degeneration. Among the neurodegeneration with brain iron accumulation disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2 (PANK2) which catalyzed the first reaction of the coenzyme A biosynthesis pathway. Currently there is no effective treatment to prevent the inexorable course of these disorders. The aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in PKAN. Recently, we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules, mitochondrial dysfunction and a pronounced increase of markers of oxidative stress. In addition, PKAN fibroblasts showed a morphological senescence-like phenotype. Interestingly, pantothenate supplementation, the substrate of the PANK2 enzyme, corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme expression. However, pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete protein. The correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN fibroblasts. Our observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in specific mutations. Fibroblasts and induced neurons derived from patients can provide a useful tool for recognizing PKAN patients who can respond to pantothenate treatment. The presence of low but significant PANK2 expression which can be increased in particular mutations gives valuable information which can support the treatment with high dose of pantothenate. The evaluation of personalized treatments in vitro of fibroblasts and neuronal cells derived from PKAN patients with a wide range of pharmacological options currently available, and monitoring its effect on the pathophysiological changes, can help for a better therapeutic strategy. In addition, these cell models will be also useful for testing the efficacy of new therapeutic options developed in the future.

Effects of rumen-protected pantothenate supplementation on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows.

Lactation performance of dairy cow has considerably increased with animal breeding and management improvement in recent years. Ruminal net synthesised pantothenic acid is insufficient to meet the requirement of high producing dairy cows. The objective was to investigate the effects of rumen-protected pantothenate (RPP) on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows. Dry matter (DM) intake tended to increase, whereas milk yields, milk fat percentage and yield, body condition score (BCS) changes and net energy output except for maintenance increased linearly with increasing RPP supplementation. Ruminal pH and ammonia N concentration tended to decrease, total VFA tended to increase, while acetate-to-propionate ratio increased linearly with increasing RPP supplementation. Digestibilities of DM, organic matter and crude protein increased linearly, but neutral detergent fibre and acid detergent fibre digestibility tended to increase. Blood glucose, total protein, non-esterified fatty acids, pantothenic acid, pantothenate kinase, succinyl CoA, acyl carrier protein and acetyl CoA also increased linearly with increasing RPP supplementation. The results indicated that supplementary RPP improved lactation performance, nutrient digestion and blood parameters in a dose-dependent manner, and the optimal dose was 12 g RPP per cow per day in the current study. © 2017 Society of Chemical Industry.

Dietary pantothenic acid depressed the gill immune and physical barrier function via NF-κB, TOR, Nrf2, p38MAPK and MLCK signaling pathways in grass carp (Ctenopharyngodon idella).

This study explored the effects of pantothenic acid (PA) on the immune and physical barrier function, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella). The results indicated that compared with optimal PA supplementation, PA deficiency (1.31 mg/kg diet) decreased gill interleukin 10, transforming growth factor β1, inhibitor of κBα (IκBα), eIF4E-binding protein 2, Claudin b and ZO-1 mRNA levels; anti-superoxide anion activity, and activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase, glutathione peroxidase, glutathione reductase and NF-E2-related factor (P < 0.05). Additionally, PA deficiency and excess (75.08 mg/kg diet) decreased gill complement 3 and glutathione contents, lysozyme and acid phosphatase, anti-hydroxy radical, catalase and glutathione S-transferases activities, and liver-expression antimicrobial peptide 2, hepcidin, Claudin 3, Claudin c and Occludin mRNA levels (P < 0.05). Conversely, PA deficiency increased gill reactive oxygen species and protein carbonyl contents, and interferon γ2, interleukin 8, nuclear factor kappa B P65, Claudin 15a, Kelch-like ECH-associating protein 1a and Kelch-like ECH-associating protein 1b mRNA levels (P<0.05). Moreover, PA deficiency and excess increased gill malondialdehyde content, and tumor necrosis factor α, interleukin 1β, IκB kinase α, IκB kinase β, IκB kinase γ, target of rapamycin and ribosomal S6 protein kinase1 p38 mitogen-activated protein kinases and myosin light-chain kinase mRNA levels (P<0.05). In conclusion, PA deficiency decreased immune and physical barrier function, and regulated relative mRNA levels of signaling molecules in fish gill. Based on the quadratic regression analysis of gill lysozyme activity, the optimal PA levels in grass carp (253.44-745.25 g) were estimated to be 36.97 mg/kg diet.

Effect of biotin and pantothenic acid on performance and concentrations of avidin-binding substances in blood and milk of lactating dairy cows

We hypothesized that pantothenic acid reduces the absorption of biotin in lactating dairy cows. Therefore, the objective of this study was to evaluate the plausible interaction between biotin and pantothenic acid on production performance and concentration of avidin-binding substances (ABS), an indicator of biotin concentration, in blood and milk of lactating dairy cows. Eight primiparous and 16 multiparous Holstein cows were assigned to 1 of 4 diet sequences in a replicated 4×4 Latin square design with 18-d periods. Cows were housed in a freestall barn and fed once daily (0730 h) by means of a Calan gate system (American Calan Inc., Northwood, NH). Treatments consisted of a control diet that contained no B-vitamins, a biotin diet that contained 0.87 mg of biotin per kilogram of dry matter (DM), a pantothenic acid diet that contained 21 mg of pantothenic acid per kilogram of DM, and a biotin plus pantothenic acid diet that contained 0.87 mg of biotin and 21 mg of calcium pantothenic acid per kilogram of DM. Four different concentrates were prepared in a commercial feed mill. These concentrates were mixed with corn silage and grass hay and delivered ad libitum as a total mixed ration. Biotin supplementation did not affect DM intake, milk yield, or milk fat, protein, lactose, and milk-urea-nitrogen concentrations. Fat, protein, and lactose yields were not affected by treatments. The fat-to-protein ratio was <1 and similar among all treatments. Biotin supplementation did not increase the concentration of ABS in plasma. The supplementation of pantothenic acid did not affect the concentration of ABS in plasma when either supplemented alone or in combination with biotin. Biotin supplementation increased the concentration of ABS in milk relative to control. Contrary to our hypothesis, the supplementation of pantothenic acid did not decrease the concentration of ABS in milk relative to the control. When cows were supplemented with both biotin and pantothenic acid, the concentration of ABS in milk was similar to that of cows supplemented with biotin alone. In conclusion, pantothenic acid did not affect the concentrations of ABS in plasma and milk, suggesting that increasing dietary supply of pantothenic acid did not inhibit biotin absorption.

Dietary pantothenic acid deficiency and excess depress the growth, intestinal mucosal immune and physical functions by regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in grass carp (Ctenopharyngodon idella)

This study investigated the effects of dietary pantothenic acid (PA) on the growth, intestinal mucosal immune and physical barrier, and relative mRNA levels of signaling molecules in the intestine of grass carp (Ctenopharyngodon idella). A total of 540 grass carp (253.44 ± 0.69 g) were fed six diets with graded levels of PA (PA1, PA15, PA30, PA45, PA60 and PA75 diets) for 8 weeks. The results indicated that compared with PA deficiency (PA1 diet) and excess (PA75 diet) groups, optimal PA supplementation increased (P < 0.05): (1) percent weight gain (PWG), feed intake and feed efficiency; (2) lysozyme activity, complement 3 content, liver-expressed antimicrobial peptide 2 and hepcidin, interleukin 10, transforming growth factor β1 and inhibitor of κBα mRNA levels in some intestinal segments; (3) activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferases and glutathione reductase, and NF-E2-related factor 2 (Nrf2) mRNA level in the whole intestine; (4) Claudin b, Claudin 3, Claudin c, Occludin and ZO-1 mRNA levels in some intestinal segments of grass carp. Conversely, optimal PA supplementation decreased (P < 0.05): (1) tumor necrosis factor α, interleukin 1β, interferon γ2, interleukin 8, nuclear factor κB P65 (NF-κB P65), IκB kinase α, IκB kinase β, IκB kinase γ and target of rapamycin (TOR) mRNA expression levels in some intestinal segments; (2) reactive oxygen species, malondialdehyde and protein carbonyl contents, and Kelch-like ECH-associating protein 1a, Kelch-like ECH-associating protein 1b in the intestine; (3) Claudin 12, Claudin 15a and myosin light-chain kinase (MLCK) mRNA levels in some intestinal segments of grass carp. In conclusion, optimum PA promoted growth, intestinal mucosal immune and physical function, as well as regulated mRNA levels of signaling molecules NF-κB P65, TOR, Nrf2 and MLCK in grass carp intestine. Based on the quadratic regression analysis of PWG and intestinal lysozyme activity, the optimal PA levels in grass carp (253.44–745.25 g) were estimated to be 37.73 mg/kg and 41.38 mg/kg diet, respectively.

Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia.

Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide-induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease.

Pantothenate and pantetheine antagonize the antitubercular activity of pyrazinamide.

Pyrazinamide (PZA) is a first-line tuberculosis drug that inhibits the growth of Mycobacterium tuberculosis via an as yet undefined mechanism. An M. tuberculosis laboratory strain that was auxotrophic for pantothenate was found to be insensitive to PZA and to the active form, pyrazinoic acid (POA). To determine whether this phenotype was strain or condition specific, the effect of pantothenate supplementation on PZA activity was assessed using prototrophic strains of M. tuberculosis. It was found that pantothenate and other β-alanine-containing metabolites abolished PZA and POA susceptibility, suggesting that POA might selectively target pantothenate synthesis. However, when the pantothenate-auxotrophic strain was cultivated using a subantagonistic concentration of pantetheine in lieu of pantothenate, susceptibility to PZA and POA was restored. In addition, we found that β-alanine could not antagonize PZA and POA activity against the pantothenate-auxotrophic strain, indicating that the antagonism is specific to pantothenate. Moreover, pantothenate-mediated antagonism was observed for structurally related compounds, including n-propyl pyrazinoate, 5-chloropyrazinamide, and nicotinamide, but not for nicotinic acid or isoniazid. Taken together, these data demonstrate that while pantothenate can interfere with the action of PZA, pantothenate synthesis is not directly targeted by PZA. Our findings suggest that targeting of pantothenate synthesis has the potential to enhance PZA efficacy and possibly to restore PZA susceptibility in isolates with panD-linked resistance.

Use of pantothenate as a metabolic switch increases the genetic stability of farnesene producing Saccharomyces cerevisiae

We observed that removing pantothenate (vitamin B5), a precursor to co-enzyme A, from the growth medium of Saccharomyces cerevisiae engineered to produce β-farnesene reduced the strain׳s farnesene flux by 70%, but increased its viability, growth rate and biomass yield. Conversely, the growth rate and biomass yield of wild-type yeast were reduced. Cultivation in media lacking pantothenate eliminates the growth advantage of low-producing mutants, leading to improved production upon scale-up to lab-scale bioreactor testing. An omics investigation revealed that when exogenous pantothenate levels are limited, acyl-CoA metabolites decrease, β-oxidation decreases from unexpectedly high levels in the farnesene producer, and sterol and fatty acid synthesis likely limits the growth rate of the wild-type strain. Thus pantothenate supplementation can be utilized as a “metabolic switch” for tuning the synthesis rates of molecules relying on CoA intermediates and aid the economic scale-up of strains producing acyl-CoA derived molecules to manufacturing facilities.

Effects of pantothenic acid supplement on secretion of steroids by the adrenal cortex in female rats.

The effect of pantothenic acid (PaA) supplementation on adrenal secretion of corticosterone and progesterone in female rats was investigated. An in-vitro primary adrenal cell culture system was used. Pregnant rats were given 0.03% PaA in their drinking water throughout pregnancy and the period of lactation. In the first experiment, after weaning, female rats continued to receive 0.03% PaA treatment until 10 weeks of age. The animals were then decapitated and adrenal cells were cultured in the absence or presence of rat adrenocorticotropic hormone (ACTH) for 4 h. In the second experiment, adrenal cells from lactating rats on day 5 of lactation were cultured in the absence or presence of rat ACTH for 4 h. The effect of ACTH at 10-10 m on corticosterone and progesterone release was greater for PaA-treated cyclic rats than for control cyclic rats. The effect of ACTH at 10-10 m on corticosterone release was greater for PaA-treated lactating rats than for control lactating rats. Circulating ACTH and corticosterone levels in PaA-treated and control cyclic and lactating rats were no different. These results indicate that PaA supplementation induced hyperresponsiveness to ACTH stimulation in cyclic and lactating female rats. These results clearly demonstrated that PaA is an essential factor in adrenal steroidogenesis of female rats.

Acute pantothenic acid and cysteine supplementation does not affect muscle coenzyme A content, fuel selection, or exercise performance in healthy humans

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.