UNASSIGNED: Localized pantothenic acid deficiencies have been observed in several neurodegenerative diseases such as Alzheimer\'s disease (AD), Parkinson\'s disease dementia (PDD), and Huntington\'s disease (HD), indicating downstream energetic pathway perturbations. However, no studies have yet been performed to see whether such deficiencies occur across the dementia with Lewy bodies (DLB) brain, or what the pattern of such dysregulation may be.
UNASSIGNED: Firstly, this study aimed to quantify pantothenic acid levels across ten regions of the brain in order to determine the localization of any pantothenic acid dysregulation in DLB. Secondly, the localization of pantothenic acid alterations was compared to that previously in AD, PDD, and HD brains.
UNASSIGNED: Pantothenic acid levels were determined in 20 individuals with DLB and 19 controls by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) across ten brain regions. Case-control differences were determined by nonparametric Mann-Whitney U test, with the calculation of S-values, risk ratios, E-values, and effect sizes. The results were compared with those previously obtained in DLB, AD, and HD.
UNASSIGNED: Pantothenic acid levels were significantly decreased in six of the ten investigated brain regions: the pons, substantia nigra, motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. This level of pantothenic acid dysregulation is most similar to that of the AD brain, in which pantothenic acid is also decreased in the motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. DLB appears to differ from other neurodegenerative diseases in being the only of the four to not show pantothenic acid dysregulation in the cerebellum.
UNASSIGNED: Pantothenic acid deficiency appears to be a shared mechanism of several neurodegenerative diseases, although differences in the localization of this dysregulation may contribute to the differing clinical pathways observed in these conditions.
Decreases in a molecule called pantothenic acid (also known as vitamin B5) have been observed in several areas of the brain in multiple dementia disease, including Alzheimer’s disease, Parkinson’s disease dementia, and Huntington’s disease. However, it is unknown whether such changes also occur in another dementia disease, dementia with Lewy bodies, which shows many of the same symptoms and molecular changes as these conditions. As such, this study was performed in order to determine if and where changes in pantothenic acid occur throughout the dementia with Lewy bodies brain. Using a methodology called liquid chromatography–mass spectrometry, which is able to measure pantothenic acid levels in a highly precise manner in brain tissues, we found that several regions of the dementia with Lewy bodies brain show decreases in pantothenic acid, including some involved in movement such as the substantia nigra and motor cortex, as well as regions associated with cognition and memory such as the hippocampus—looking most similar to the pattern of changes already seen in Alzheimer’s disease. It is possible that these changes contribute to the progression of dementia with Lewy bodies; however, further studies need to be performed to determine at what point these changes happen during the disease and how they may contribute to the development of symptoms.

This study explored the effects of different vitamin B5 (VB5) levels on intestinal growth and function of weaned piglets. Twenty-one piglets (7.20 ± 1.11 kg) were included in a 28-day feeding trial with three treatments, including 0 mg/kg (L-VB5), 10 mg/kg (Control) and 50 mg/kg (H-VB5) of VB5 supplement. The results showed that: Large intestine weight/body weight was the highest in H-VB5 group, Control and H-VB5 groups had significantly higher villus height and villus height/crypt depth than the L-VB5 in the ileum (p < .05). Goblet cells (ileal crypt) and endocrine cells (ileal villus) significantly increased in Control and H-VB5 (p < .05). The H-VB5 group exhibited significantly higher levels of ki67 and crypt depth in the cecum and colon, colonic goblet cells and endocrine cells were both rising considerably (p < .05). Isobutyric acid and isovaleric acid were significantly reduced in the H-VB5 group (p < .05), and there was a decreasing trend in butyric acid (p = .073). At the genus level, the relative abundance of harmful bacteria such as Clostridium_Sensu_Structo_1 Strecto_1, Terrisporbacter and Streptococcus decreased significantly and the relative abundance of beneficial bacteria Turicibacter increased significantly in H-VB5 group (p < .05). Overall, the addition of 50 mg/kg VB5 primarily enhanced the morphological structure, cell proliferation and differentiation of the ileum, cecum and colon. It also had a significant impact on the gut microbiota and short-chain fatty acids.

Salt stress negatively affects rice growth, development and yield. Metabolic adjustments contribute to the adaptation of rice under salt stress. Branched-chain amino acids (BCAA) are three essential amino acids that cannot be synthesized by humans or animals. However, little is known about the role of BCAA in response to salt stress in plants. Here, we showed that BCAAs may function as scavengers of reactive oxygen species (ROS) to provide protection against damage caused by salinity. We determined that branched-chain aminotransferase 2 (OsBCAT2), a protein responsible for the degradation of BCAA, positively regulates salt tolerance. Salt significantly induces the expression of OsBCAT2 rather than BCAA synthesis genes, which indicated that salt mainly promotes BCAA degradation and not de novo synthesis. Metabolomics analysis revealed that vitamin B5 (VB5) biosynthesis pathway intermediates were higher in the OsBCAT2-overexpressing plants but lower in osbcat2 mutants under salt stress. The salt stress-sensitive phenotypes of the osbcat2 mutants are rescued by exogenous VB5, indicating that OsBCAT2 affects rice salt tolerance by regulating VB5 synthesis. Our work provides new insights into the enzymes involved in BCAAs degradation and VB5 biosynthesis and sheds light on the molecular mechanism of BCAAs in response to salt stress.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare and complex neurodegenerative disorder. It occurs due to mutations in the sequencing of the PANK2 gene. Here, we describe the case of a 22-year-old male patient who presented with severe blepharospasm; he had abnormal facial distortions, shaky limbs, rigid muscles, and a slow pace of movement, making a diagnosis tricky. Accumulation of iron in excessive amounts in the basal ganglia, a part of the brain that governs movement, is linked to PKAN. In this case, the \"eye of the tiger\" indication, a distinctive pattern only seen by MRI, supported PKAN. The anticholinergic medications helped him alleviate his symptoms to some extent, but he still had some degree of impairment. This instance emphasizes the mysterious character of PKAN and the significance of keeping an eye out for unusual symptoms in neurodegenerative conditions. This case report emphasizes the significance of recognizing unexpected effects that brain disorders can have on people\'s lives and calls for increased clinician awareness and understanding.

Malaria parasites must acquire all necessary nutrients from the vertebrate and mosquito hosts to successfully complete their life cycle. Failure to acquire these nutrients can limit or even block parasite development and presents a novel target for malaria control. One such essential nutrient is pantothenate, also known as vitamin B5, which the parasite cannot synthesize de novo and is required for the synthesis of coenzyme A (CoA) in the parasite. This review examines pantothenate and the CoA biosynthesis pathway in the human-mosquito-malaria parasite triad and explores possible approaches to leverage the CoA biosynthesis pathway to limit malaria parasite development in both human and mosquito hosts. This includes a discussion of sources for pantothenate for the mosquito, human, and parasite, examining the diverse strategies used by the parasite to acquire substrates for CoA synthesis across life stages and host resource pools and a discussion of drugs and alternative approaches being studied to disrupt CoA biosynthesis in the parasite. The latter includes antimalarial pantothenate analogs, known as pantothenamides, that have been developed to target this pathway during the human erythrocytic stages. In addition to these parasite-targeted drugs, we review studies of mosquito-targeted allosteric enzymatic regulators known as pantazines as an approach to limit pantothenate availability in the mosquito and subsequently deprive the parasite of this essential nutrient.

UNASSIGNED: Pantothenate (vitamin B5) is a precursor for coenzyme A (CoA) synthesis, which serves as a cofactor for hundreds of metabolic reactions. Cysteine is an amino acid in the CoA synthesis pathway. To date, research on the combined role of early life pantothenate and cysteine levels in childhood neurodevelopmental disabilities is scarce.
UNASSIGNED: To study the association between cord pantothenate and cysteine levels and risk of autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and other developmental disabilities (DD) in children born term and preterm.
UNASSIGNED: The study sample (n = 996, 177 born preterm) derived from the Boston Birth Cohort included 416 neurotypical children, 87 ASD, 269 ADHD, and 224 other DD children, who were mutually exclusive. Participants were enrolled at birth and were followed up prospectively (from October 1, 1998, to June 30, 2018) at the Boston Medical Center. Cord blood sample was collected at birth. Plasma pantothenate and cysteine levels were measured using liquid chromatography-tandem mass spectrometry.
UNASSIGNED: Higher cord pantothenate (≥50th percentile vs. <50th percentile) was associated with a greater risk of ASD (adjusted odds ratio [aOR]: 1.94, 95% confidence interval [CI]: 1.06, 3.55) and ADHD (aOR: 1.66, 95% CI: 1.14, 2.40), after adjusting for potential confounders. However, cord cysteine alone was not associated with risk of ASD, ADHD, or other DD. When considering the joint association, greater ASD risk was noted when both cord pantothenate and cysteine levels were elevated (≥50th percentile) (aOR: 3.11, 95% CI: 1.24, 7.79), when compared to children with low cord pantothenate (<50th percentile) and high cysteine. Even though preterm and higher pantothenate independently increased the ASD risk, the greatest risk was found in preterm children who also had elevated pantothenate (≥50th percentile), which was true for all three outcomes: ASD (aOR: 5.36, 95% CI: 2.09, 13.75), ADHD (aOR: 3.31, 95% CI: 1.78, 6.16), and other DD (aOR: 3.39, 95% CI: 1.85, 6.24).
UNASSIGNED: In this prospective birth cohort, we showed that higher cord pantothenate individually and in combination with higher cysteine or preterm birth were associated with increased risk of ASD and ADHD. More study is needed to explore this biologically plausible pathway.

Coenzyme A (CoA) serves as a vital cofactor in numerous enzymatic reactions involved in energy production, lipid metabolism, and synthesis of essential molecules. Dysregulation of CoA-dependent metabolic pathways can contribute to chronic diseases, such as inflammatory diseases, obesity, diabetes, cancer, and cardiovascular disorders. Additionally, CoA influences immune cell activation by modulating the metabolism of these cells, thereby affecting their proliferation, differentiation, and effector functions. Targeting CoA metabolism presents a promising avenue for therapeutic intervention, as it can potentially restore metabolic balance, mitigate chronic inflammation, and enhance immune cell function. This might ultimately improve the management and outcomes for these diseases. This review will more specifically focus on the contribution of pathways regulating the availability of the CoA precursor Vitamin B5/pantothenate in vivo and modulating the development of Th17-mediated inflammation, CD8-dependent anti-tumor immunity but also tissue repair processes in chronic inflammatory or degenerative diseases.

Vitamin B5, also called d-pantothenic acid, is an essential vitamin in the human body and is widely used in pharmaceuticals, nutritional supplements, food, and cosmetics. However, few studies have investigated the microbial production of d-pantothenic acid, especially in Saccharomyces cerevisiae. By employing a systematic optimization strategy, we screened seven key genes in d-pantothenic acid biosynthesis from diverse species, including bacteria, yeast, fungi, algae, plants, animals, etc., and constructed an efficient heterologous d-pantothenic acid pathway in S. cerevisiae. By adjusting the copy number of the pathway modules, knocking out the endogenous bypass gene, balancing NADPH utilization, and regulating the GAL inducible system, a high-yield d-pantothenic acid-producing strain, DPA171, which can regulate gene expression using glucose, was constructed. By optimizing fed-batch fermentation, DPA171 produced 4.1 g/L d-pantothenic acid, which is the highest titer in S. cerevisiae to date. This study provides guidance for the development of vitamin B5 microbial cell factories.

Human PANK1, PANK2, and PANK3 genes encode several pantothenate kinase isoforms that catalyze the phosphorylation of vitamin B5 (pantothenic acid) to phosphopantothenate, a critical step in the biosynthesis of the major cellular cofactor, Coenzyme A (CoA). Mutations in the PANK2 gene, which encodes the mitochondrial pantothenate kinase (PanK) isoform, have been linked to pantothenate-kinase associated neurodegeneration (PKAN), a debilitating and often fatal progressive neurodegeneration of children and young adults. While the biochemical properties of these enzymes have been well-characterized in vitro, their expression in a model organism such as yeast in order to probe their function under cellular conditions have never been achieved. Here we used three yeast mutants carrying missense mutations in the yeast PanK gene, CAB1, which are associated with defective growth at high temperature and iron, mitochondrial dysfunction, increased iron content, and oxidative stress, to assess the cellular function of human PANK genes and functional conservation of the CoA-controlled processes between humans and yeast. Overexpression of human PANK1 and PANK3 in these mutants restored normal cellular activity whereas complementation with PANK2 was partial and could only be achieved with an isoform, PanK2mtmΔ, lacking the mitochondrial transit peptide. These data, which demonstrate functional conservation of PanK activity between humans and yeast, set the stage for the use of yeast as a model system to investigate the impact of PKAN-associated mutations on the metabolic pathways altered in this disease.

Mutations in the Transport and Golgi Organization 2 (TANGO2) gene are associated with intellectual deficit, neurodevelopmental delay and regression. Individuals can also present with an acute metabolic crisis that includes rhabdomyolysis, cardiomyopathy, and cardiac arrhythmias, the latter of which are potentially lethal. While preventing metabolic crises has the potential to reduce mortality, no treatments currently exist for this condition. The function of TANGO2 remains unknown but is suspected to be involved in some aspect of lipid metabolism. Here, we describe a model of TANGO2-related disease in the fruit fly Drosophila melanogaster that recapitulates crucial disease traits. Pairing a new fly model with human cells, we examined the effects of vitamin B5, a coenzyme A (CoA) precursor, on alleviating the cellular and organismal defects associated with TANGO2 deficiency. We demonstrate that vitamin B5 specifically improves multiple defects associated with TANGO2 loss-of-function in Drosophila and rescues membrane trafficking defects in human cells. We also observed a partial rescue of one of the fly defects by vitamin B3, though to a lesser extent than vitamin B5. Our data suggest that a B complex supplement containing vitamin B5/pantothenate may have therapeutic benefits in individuals with TANGO2-deficiency disease. Possible mechanisms for the rescue are discussed that may include restoration of lipid homeostasis.