Article
Endocrinology & Metabolism
Mei Xue
Summary: This case report describes the first case of type B pyruvate carboxylase deficiency in China. The patient presented with intractable lactic acidosis shortly after birth and prenatal neuroradiological presentations were observed. Despite treatment, the infant died at 26 days.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Caroline E. Nunes-Xavier, Janire Mingo, Maite Emaldi, Karine Flem-Karlsen, Gunhild M. Maelandsmo, Oystein Fodstad, Roberto Llarena, Jose I. Lopez, Rafael Pulido
Summary: This study revealed heterogeneous expression of PDH complex components in PCa tumors, with PDH complex components being related to AR signaling and PDK2 expression associated with poor PCa prognosis. These findings highlight the potential of targeting PDH complex components for intervention in PCa.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
David L. Long, Charles E. McCall, Leslie B. Poole
Summary: This study demonstrates that LPS induces reversible oxidation within PDCE2 in THP-1 cells and primary human monocytes. Glutathionylation is associated with wild type PDCE2 but not mutant protein lacking the lipoamide-linking lysine residues. The combination treatment of LPS and MitoCDNB has a synergistic effect on PDCE2 glutathionylation, ROS production, and cell death, while showing differential effects on cytokine production.
Review
Nutrition & Dietetics
Zhenhua Zeng, Qiaobing Huang, Liangfeng Mao, Jie Wu, Sheng An, Zhongqing Chen, Weijin Zhang
Summary: Anaerobic glycolysis is the primary metabolic pathway in sepsis, and the PDHC complex plays a crucial role in energy metabolism. Activation of PDHC can regulate lactate balance, inflammatory mediator release, and improve energy metabolism. Therapeutic drugs targeting PDHC activation for sepsis treatment include dichloroacetate, thiamine, and others.
FRONTIERS IN NUTRITION
(2021)
Article
Genetics & Heredity
Anisha Verma, April N. Lehman, Hatice Gokcan, Lorna Cropcho, Danielle Black, Steven F. Dobrowolski, Jerry Vockley, Jirair K. Bedoyan
Summary: Pyruvate dehydrogenase complex deficiency (PDCD) is a mitochondrial neurometabolic disorder with high incidence. The use of specific amino acid ratio combinations as biomarkers can effectively identify patients with PDCD.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Multidisciplinary Sciences
Eduardo M. Bruch, Pierre Vilela, Lu Yang, Alexandra Boyko, Norik Lexa-Sapart, Bertrand Raynal, Pedro M. Alzari, Marco Bellinzoni
Summary: This study reveals a unique structure of alpha-oxoacid dehydrogenase complexes in Actinobacteria, defying the traditional high-molecular weight core structure. This feature, possibly reflecting the association of PDH and ODH into a single physical complex, paves the way for therapeutic and metabolic engineering applications concerning the central nodes of pyruvate and 2-oxoglutarate in central metabolism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Nicholas L. Arp, Gretchen L. Seim, James A. Votava, Jordyn Josephson, Jing Fan
Summary: This study revealed a new mechanism for BCKDC regulation and demonstrated the broad inhibitory effects of RNS on all alpha-ketoacid dehydrogenases. It has significant physiological implications for multiple cell types and elucidates the mechanistic connection between RNS-driven inhibitory modifications on the E2 and E3 subunits of alpha-ketoacid dehydrogenases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Nutrition & Dietetics
Orna Staretz-Chacham, Ben Pode-Shakked, Eyal Kristal, Smadar Yaala Abraham, Keren Porper, Ohad Wormser, Ilan Shelef, Yair Anikster
Summary: Partial KD treatment can improve the survival of patients with DLD-E3 deficiency, but it does not significantly improve the quality of life (QOL) of the patients.
Article
Medicine, Research & Experimental
Jiyoung Oh, Chungmo Koo, Kyung Won Kim, Jin-Sung Lee
Summary: PDH deficiency is an inherited metabolic disorder caused by a defect in the pyruvate dehydrogenase complex, with stress-induced gluconeogenesis potentially contributing to rapid disease exacerbation.
MEDICAL HYPOTHESES
(2021)
Article
Biochemistry & Molecular Biology
Yuan Zhou, Meng Cai, Huan Zhou, Leifeng Hou, Hao Peng, Hongwu He
Summary: Computer aided optimization was utilized to design a series of new agrochemical compounds, which exhibited excellent inhibitory activity against Escherichia coli. Compound 6l showed the best inhibitory activity with an IC50 value of 95 nM. In vitro antibacterial activity tests showed that some compounds exhibited higher inhibition against Ralstonia solanacearum compared to commercial chemical pesticides.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hana Pavlu-Pereira, Diana Lousa, Catarina S. Tome, Cristina Florindo, Maria Joao Silva, Isabel Tavares de Almeida, Paula Leandro, Isabel Rivera, Joao B. Vicente
Summary: Pyruvate dehydrogenase complex (PDC) deficiency is a metabolic disorder with a wide range of symptoms, mainly caused by mutations affecting the PDHA1 gene encoding the a subunit of the PDC-E1 component. Detailed analysis of pathogenic protein variants shows functional impairment and decreased stability, posing challenges for developing therapies.
Article
Endocrinology & Metabolism
Antri Savvidou, Liz Ivarsson, Karin Naess, Erik A. Eklund, Johan Lundgren, Maria Dahlin, Deborah Frithiof, Kalliopi Sofou, Niklas Darin
Summary: The diverse clinical and radiological spectrum of pyruvate dehydrogenase complex (PDHc) deficiency presents challenges in diagnostics and disease monitoring. A timely diagnosis is crucial for initiating a ketogenic diet early. This study in Sweden found that the most common MRI findings in genetically confirmed PDHc deficiency patients were agenesis or hypoplasia of corpus callosum, ventriculomegaly, or Leigh-like lesions. Notably, the simultaneous presence of multiple lesions on MRI scans occurring during different phases of brain development could be a key indicator of PDHc deficiency.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Nutrition & Dietetics
Ryan Atkins, Dumitru Constantin-Teodosiu, Krishna K. Varadhan, Despina Constantin, Dileep N. Lobo, Paul L. Greenhaff
Summary: This post hoc study found that major elective abdominal surgery had an acute impact on mitochondrial pyruvate dehydrogenase complex (PDC) activity and maximal mitochondrial ATP production rates (MAPR) in a distant muscle group. Muscle PDC activity was reduced by 50% at the end of surgery, and muscle MAPR were comprehensively suppressed by surgery for various substrate combinations. These findings suggest that general anesthesia and surgery-related trauma may be drivers of muscle metabolic insult.
CLINICAL NUTRITION
(2021)
Article
Biochemistry & Molecular Biology
Raquel Vaz, Josephine Wincent, Najla Elfissi, Kristina Rosengren Forsblad, Maria Pettersson, Karin Naess, Anna Wedell, Anna Wredenberg, Anna Lindstrand, Sofia Ygberg
Summary: This study reported a de novo heterozygous missense variant in the PDK1 gene in a girl with developmental delay and early onset severe epilepsy. Using a zebrafish model, the study showed the impact of this variant on energy metabolism and neuronal development, and the possible mechanism behind the clinical symptoms.
Review
Multidisciplinary Sciences
Dirk Roosterman, Graeme Stuart Cottrell
Summary: This article introduces two complexes in Krebs' Citric Acid Cycle, namely Citric Acid Cycle 1.1 and Citric Acid Cycle 2.1. Citric Acid Cycle 1.1 is regulated by NAD+ and involves lactate as substrate and malate as product, while Citric Acid Cycle 2.1 is regulated by FAD and involves malate as substrate and succinate or citrate as products. These complexes balance stress and accelerate ATP recovery in cells, with Citric Acid Cycle 2.1 playing a role in energy storage in white adipocytes.