405 results match your criteria: "Pyruvate Carboxylase Deficiency"
Compensatory activity of the PC-ME1 metabolic axis underlies differential sensitivity to mitochondrial complex I inhibition.
Nat Commun
October 2024
Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), Madrid, Spain.
Article Synopsis
- Deficiencies in the electron transport chain (ETC) contribute to mitochondrial diseases, but the reasons for different cellular sensitivities to this disruption are not fully understood.
- This study finds that under ETC inhibition, a different type of tricarboxylic acid (TCA) cycle is activated to maintain malate levels and produce NADPH, which is crucial for cell function.
- The research highlights how astrocytes, which express specific enzymes like Pyruvate carboxylase (PC) and ME1 more than neurons, demonstrate greater resilience to ETC issues, suggesting potential therapeutic strategies for managing mitochondrial diseases.
Article Synopsis
- Pyruvate carboxylase deficiency is a rare genetic condition affecting the enzyme that converts pyruvate to oxaloacetate, leading to three clinical phenotypes: neonatal type A, infantile type B, and a benign type C.
- This case series documents three Sri Lankan neonates, including two siblings, who exhibited respiratory distress at birth, with one sibling showing typical signs of type B and the other exhibiting unique characteristics of type A.
- The study emphasizes the importance of quick lab tests in newborns with breathing difficulties and metabolic issues for better management and family support, urging for more research on the overlapping symptoms of the different phenotypes.
Staphylococcal aconitase expression during iron deficiency is controlled by an sRNA-driven feedforward loop and moonlighting activity.
Nucleic Acids Res
August 2024
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France.
Article Synopsis
- Pathogenic bacteria like Staphylococcus aureus use regulatory RNA (sRNA) called IsrR to adapt to low iron conditions and maintain virulence.
- IsrR helps conserve iron by down-regulating genes for iron-containing enzymes, particularly affecting the tricarboxylic acid (TCA) cycle and the enzyme aconitase.
- Aconitase also acts as a regulatory protein that influences its own expression and modulates the expression of other enzymes, thereby helping the bacteria cope with iron scarcity.
Meta-analysis of transcriptomic profiles in reveals molecular pathway responses to different abiotic stresses.
Funct Plant Biol
February 2024
Department of Food Biotechnology, Branch for Northwest & West Region, Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education and Extension Organization (AREEO), Tabriz, Iran.
Article Synopsis
- - Microalgae like Dunaliella tertiolecta are promising for sustainable metabolite production, but their responses to stress (like high light, nitrogen deficiency, and high salinity) can impact metabolite pathways.
- - The study found that stress conditions led to downregulation of certain pathways (like light reactions and lipid metabolism) and identified key enzymes that were upregulated under these stresses.
- - Results indicated a network of stress-specific gene modules, showing interconnectedness of photosynthesis and metabolism pathways, which could be useful for future research to optimize metabolite production in these microalgae.
The opposite role of lactate dehydrogenase a (LDHA) in cervical cancer under energy stress conditions.
Free Radic Biol Med
March 2024
National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130117, China. Electronic address:
Article Synopsis
- Insufficient blood supply in tumors often leads to a lack of nutrients, and LDHA is known to support tumor growth by enhancing glycolysis; however, its role in cell survival during nutrient scarcity is not well understood.
- The study found that inhibiting LDHA reduced cell survival and proliferation in cervical cancer cells under normal conditions, but promoted survival and tumor formation under energy stress from glucose starvation.
- Mechanistic investigations revealed that LDHA knockdown shifted glucose metabolism from glycolysis to mitochondrial processes, increased pyruvate accumulation, activated AMPK, and improved mitochondrial function, suggesting that targeting LDHA may not be an effective treatment strategy for cervical cancer due to its complex role in energy stress.
Article Synopsis
- Pyruvate carboxylase is a crucial enzyme involved in important metabolic pathways, and its deficiency can lead to severe neurological issues, particularly in types A and B, while type C presents more mildly.
- The treatment with triheptanoin, an odd-chain triglyceride, shows promise for replenishing essential metabolites but has had mixed results in more severe cases.
- In a study of two type C patients, triheptanoin treatment improved health outcomes, reduced hospitalizations, and enhanced brain myelination, suggesting its potential effectiveness for managing this condition.
In silico Analysis of Two Novel Variants in the Pyruvate Carboxylase (PC) Gene Associated with the Severe Form of PC Deficiency.
Iran Biomed J
September 2023
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Pasteur St., Tehran, Iran.
Article Synopsis
- Inborne errors of metabolism can lead to neonatal deaths, and this study focused on two unrelated neonates experiencing acute metabolic issues and death.
- Researchers used whole-exome sequencing and other methods to identify genetic variants in the pyruvate carboxylase gene, revealing two variants: one likely pathogenic and another of uncertain significance.
- The findings suggest that these genetic variants are responsible for type B Pyruvate carboxylase deficiency, offering potential for prenatal diagnosis and expanding knowledge of the PC gene for medical professionals.
Comprehensive isotopomer analysis of glutamate and aspartate in small tissue samples.
Cell Metab
October 2023
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:
Article Synopsis
- Stable isotopes help assess metabolism, and the new MS method can identify all isotopomers of aspartate and glutamate using less than 1% of the sample required for NMR.
- This method improves the specificity in distinguishing between metabolic pathways that yield the same count of carbon labels in these amino acids.
- The approach reveals metabolic differences in human tumors and the role of fumarate hydratase deficiency in renal cancers, enhancing in vivo isotope-labeling studies.
Case Report: Prenatal neurological injury in a neonate with pyruvate carboxylase deficiency type B.
Front Endocrinol (Lausanne)
July 2023
Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Background: Pyruvate carboxylase (PC) is a key enzyme for gluconeogenesis. PC deficiency (PCD) is an extremely rare autosomal recessive metabolic disease and is divided into three types. Type B PCD is clinically featured by lactic acidosis, hyperammonemia, hypercitrullinemia, hypotonia, abnormal movement, and seizures.
View Article and Find Full Text PDFHuman IP receptor triple knockout stem cells remain pluripotent despite altered mitochondrial metabolism.
Cell Calcium
September 2023
Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, 00290, Finland; Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, 00290, Finland. Electronic address:
Article Synopsis
- Inositol 1,4,5-trisphosphate receptors (IPRs) are crucial channels in cells that help manage various processes, and their absence in animal models leads to serious developmental issues.* -
- Researchers created knockouts of IPRs in human induced pluripotent stem cells (hiPSCs), finding that while these knockouts didn't generate calcium signals when activated, they still maintained their stem cell qualities.* -
- Analysis revealed that the lack of IPRs altered metabolic pathways involving the tricarboxylic acid cycle, indicating IPRs play a role in regulating mitochondrial metabolism rather than stem cell identity.*
Long-term chronic food-derived arsenic exposure induce the urinary system metabolic dysfunction in mice.
Sci Total Environ
November 2023
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, Synergetic Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi, Jiangsu, PR China; Yixing Institute of Food and Biotechnology, No. 19, Wenzhuang Road, Qiting Street, Yixing City, Wuxi, China.
Article Synopsis
- * A study conducted on mice over 14 months revealed significant changes in lipid levels, with phosphatidylethanolamine increasing while other lipids decreased, indicating metabolic disruptions.
- * The findings suggest that arsenic exposure may also link to inherited metabolic disorders, with notable biomarkers detected in urine pointing to potential impacts on amino acid and energy metabolism.
Clinical, biochemical and molecular characterization of 12 patients with pyruvate carboxylase deficiency treated with triheptanoin.
Mol Genet Metab
June 2023
Division of Genetic and Genomic Medicine, UPMC Children's Hospital of Pittsburgh and Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:
Article Synopsis
- Pyruvate carboxylase (PC) deficiency is a rare genetic disorder that leads to severe health issues like lactic acidosis and neurological problems, with few treatment options available.
- Triheptanoin, an anaplerotic agent, has been tested in a small group of individuals with varying results, indicating potential but inconsistent benefits in lowering blood lactate levels and improving quality of life.
- Analysis revealed that individuals with specific mutations in the PC enzyme may respond better to triheptanoin, highlighting the need for more research to understand these differences in treatment response.
Deficiency of transcription factor Nkx6.1 does not prevent insulin secretion in INS-1E cells.
Sci Rep
January 2023
Department of Mitochondrial Physiology, No. 75, Institute of Physiology of the Czech Academy of Sciences, Vídeňská 1083, Prague, 14220, Czech Republic.
Article Synopsis
- Nkx6.1 is a crucial transcription factor for pancreatic development and β-cell function, regulating key genes involved in glucose transport and insulin processing.
- In aging diabetic rats, decreased Nkx6.1 levels can lead to β-cell trans-differentiation into different cell types, affecting insulin secretion.
- Experiments with rat INS-1E cells, where Nkx6.1 was edited out, showed that while certain gene expressions were reduced, the cells still managed to compensate for insulin secretion through alternative pathways, suggesting Nkx6.1's role isn't as critical for immediate insulin function as previously thought.
Generation of an induced pluripotent stem cell line (SHCDNi007-A) from a patient with pyruvate carboxylase deficiency carrying compound heterozygous (c.182 T > C/ c.2581G > A) variants in PC.
Stem Cell Res
February 2023
Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200062 China. Electronic address:
Article Synopsis
- Pyruvate carboxylase (PC) deficiency (PCD) is a rare genetic metabolic disorder that causes seizures, developmental delays, and metabolic issues, including high levels of lactic acid, pyruvate, and alanine.
- A new induced pluripotent stem cell line (SHCDNi007-A) was created from blood cells of a 2-month-old infant with two specific PC gene mutations.
- This new cell line aims to help researchers better understand the disease and work towards developing effective treatments for PCD.
Mitochondrial carbonic anhydrase VA and VB: properties and roles in health and disease.
J Physiol
January 2023
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Article Synopsis
- Carbonic anhydrase V (CA V) is a mitochondrial enzyme found in mammals, with two forms in mice (CA VA and CA VB) that have distinct functions in ammonia detoxification and metabolic processes.
- CA VA is crucial for detoxifying ammonia and providing bicarbonate for biosynthesis, while CA VB's role is less understood but important for spermatogenesis.
- Mutations in CA5A lead to metabolic issues in children, and early detection of hyperammonaemia can allow effective treatment with N-carbamyl-l-glutamate, making CA VA deficiency a treatable metabolic condition.
Survival Pathways of HIF-Deficient Tumour Cells: TCA Inhibition, Peroxisomal Fatty Acid Oxidation Activation and an AMPK-PGC-1α Hypoxia Sensor.
Cells
November 2022
Cancer Research UK Cambridge Institute, Cambridge University, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
Article Synopsis
- The study investigates how cancer cells may resist therapies targeting HIF-1 and HIF-2 by examining Hepa-1c4 cells that lack HIF signaling, simulating a situation where these pathways are effectively inhibited.
- HIF-1β-deficient Hepa-1c4 cells showed adaptive responses to hypoxia, increasing glucose uptake and lactate production, while also activating metabolic pathways associated with energy survival, such as the AMPK pathway.
- The research suggests that combining HIF1/2 inhibitors with PGC-1α or AMPK inhibitors could be a promising strategy to tackle cancer cells that can proliferate without relying on HIF pathways.
A Rare Case of Type B Neonatal Pyruvate Carboxylase Enzyme Deficiency Presenting With Refractory Lactic Acidosis in the Early Neonatal Period.
Cureus
October 2022
Pediatrics, Neonatal-Perinatal Medicine, Children's Hospital of Michigan/Central Michigan University College of Medicine, Detroit, USA.
Article Synopsis
- Pyruvate carboxylase (PC) deficiency is a rare genetic disorder that affects how the body metabolizes certain substances, inherited in an autosomal recessive manner.
- The disorder leads to problems in energy production and important biochemical processes, resulting in various serious health issues, including severe lactic acidosis in affected infants.
- In the case presented, a newborn with PC deficiency had alarming clinical symptoms identified through various tests, confirming the diagnosis, but ultimately passed away by day 22 after birth, despite being provided with palliative care.
Genome-Wide CRISPR/Cas9 Library Screening Revealed Dietary Restriction of Glutamine in Combination with Inhibition of Pyruvate Metabolism as Effective Liver Cancer Treatment.
Adv Sci (Weinh)
December 2022
Department of Pathology, The University of Hong Kong, Hong Kong, P. R. China.
Article Synopsis
- Hepatocellular carcinoma (HCC) is a highly lethal cancer that may be effectively targeted by limiting dietary glutamine, a nutrient that supports HCC growth.
- The study reveals that certain enzymes involved in pyruvate metabolism (PDHA, PDHB, and PC) are essential for HCC cells to adapt when glutamine is scarce, enabling rapid metabolic adjustments.
- Combining a glutamine-restricted diet with inhibitors of pyruvate metabolism shows promise in reducing HCC cell growth, suggesting a new therapeutic strategy that leverages these metabolic vulnerabilities.
[Analysis of child with pyruvate carboxylase deficiency type A due to compound heterozygous variants of the PC gene].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
September 2022
Department of Intensive Care Unit, Anhui Provincial Children's Hospital, Hefei, Anhui 230051, China.
Article Synopsis
- The study aimed to analyze the clinical symptoms and genetic factors contributing to a child diagnosed with pyruvate carboxylase deficiency type A (PCD-A).
- The child showed severe health issues, including vomiting, altered consciousness, and severe acidosis, while genetic testing identified two unique variants in the PC gene, inherited from each parent.
- The findings suggest these gene variants are likely responsible for the child's PCD-A, contributing new knowledge about genetic variations associated with this condition.
Stepwise metabolic engineering of Corynebacterium glutamicum for the production of phenylalanine.
J Gen Appl Microbiol
June 2023
Division of Agricultural Sciences, Graduate School of Sciences and Technology for Innovation, Yamaguchi University.
Article Synopsis
- Researchers engineered Corynebacterium glutamicum to enhance its production of phenylalanine, an important amino acid for food and pharmaceuticals, by modifying specific enzymes and pathways.
- Initial steps included overexpressing certain enzymes from E. coli and disabling others that negatively impacted phenylalanine production.
- The final optimized strain produced 50.7 mM of phenylalanine from glucose, opening up new possibilities for using genetically modified bacteria in the creation of valuable compounds.
Expanding the genetic spectrum of the pyruvate carboxylase deficiency with novel missense, deep intronic and structural variants.
Mol Genet Metab Rep
September 2022
Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia.
Article Synopsis
- Pathogenic variants in the pyruvate carboxylase (PC) gene can cause a variety of recessive conditions, ranging from severe early-onset disorders to milder adult forms.
- Two patient cases illustrate the genetic complexities: one boy, age 6, had a novel missense variant linked to a reciprocal translocation, while a 13-year-old girl had a different intronic variant affecting her mRNA.
- The study recommends genetic analysis of the PC gene for patients experiencing metabolic crises, emphasizing the importance of whole genome sequencing for accurate diagnosis.*
Splice-Site Variant c.1825+5G>A Caused Intron Retention in a Patient With Pyruvate Carboxylase Deficiency: A Case Report.
Front Pediatr
April 2022
Department of Pediatrics, XiJing Hospital, Fourth Military Medical University, Xi'an, China.
Background: Pyruvate carboxylase deficiency (PCD; MIM#266150) is a rare autosomal recessive disorder characterized by a wide range of clinical features, including delayed neurodevelopment, elevated pyruvate levels, lactic acidosis, elevated ketone levels, and hyperammonemia. The pyruvate carboxylase (PC) gene was identified to be the disease-causing gene for PCD. A novel homozygous splice variant in the PC gene was identified in a Chinese boy, but the pathogenicity is still unclear.
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