Review
Oncology
Ling-Chu Chang, Shih-Kai Chiang, Shuen-Ei Chen, Mien-Chie Hung
Summary: This review describes the molecular interactions, regulation, and disease relationships of OGDHc, a key enzyme in the tricarboxylic acid (TCA) cycle. Dysregulation of OGDHc can disrupt cellular redox homeostasis and lead to the accumulation of oncometabolites in cancer development. The potential of OGDHc as a therapeutic target for cancer treatment is discussed.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Review
Clinical Neurology
Haotian Liu, Yong Xie, Xia Wang, Martine Abboud, Chao Ma, Wei Ge, Christopher J. Schofield
Summary: The article discusses the potential roles of 2OGDD in AD, highlighting the relationship with synaptic dysfunction/loss and the importance of regulating neuronal/glial differentiation through enzyme activity-dependent mechanisms to protect against synaptic loss.
ALZHEIMERS & DEMENTIA
(2022)
Article
Environmental Sciences
Fan Wu, Xuexia Xie, Guoliang Li, Dongping Bao, Haomin Li, Guohao Wu, Yiqi Lai, Yaping Xing, Peng Ouyang, Guo Chen, Zhifeng Wang, Caiyong Lai
Summary: This study found that alpha-ketoglutarate (AKG) promotes autophagy in renal cancer cells by mediating the ROS-PI3K/Akt/mTOR pathway, leading to the suppression of tumor growth. This finding may provide a new potential drug for the treatment of kidney cancer.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Ling-Yue Sun, Yu-Yan Lyu, Heng-Yuan Zhang, Zhi Shen, Guan-Qiao Lin, Na Geng, Yu-Li Wang, Lin Huang, Ze-Hao Feng, Xiao Guo, Nan Lin, Song Ding, An-Cai Yuan, Lan Zhang, Kun Qian, Jun Pu
Summary: NR1D1 is upregulated in AAA tissues and its knockout in VSMCs inhibits AAA formation. NR1D1 regulates mitochondrial metabolism by repressing ACO2 expression, and α-KG supplementation has beneficial effects in preventing and treating AAA.
Article
Medicine, Research & Experimental
Junjun Liu, Mingyuan Liu, Jiaxuan Feng, Hongqiao Zhu, Jianlie Wu, Heng Zhang, Shun Xiao, Zaiping Jing, Jian Zhou, Haitao Niu, Mingjin Guo
Summary: This study reveals that alpha-ketoglutarate (AKG) can prevent and treat abdominal aortic aneurysm (AAA) through inhibiting oxidative stress and inflammation. AKG pre-treatment effectively prevents aneurysm dilation and aortic rupture, and reduces macrophage infiltration, elastin degradation, and collagen fibers remodeling. The study also demonstrates that AKG reduces the production of inflammatory cytokines, apoptosis, and excessive superoxide. Mechanistically, AKG regulates the PXDN/HOCL/ERK signaling pathway to exert its protective effects on AAA.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Richiro Ushimaru, Lide Cha, Shotaro Shimo, Xiaojun Li, Jared C. Paris, Takahiro Mori, Kazunori Miyamoto, Lindsay Coffer, Masanobu Uchiyama, Yisong Guo, Wei-chen Chang, Ikuro Abe
Summary: In this study, the catalytic mechanism and stereodivergency of BelL and HrmJ enzymes were investigated. The results showed that the nitroalkane moiety of the substrate is deprotonated to produce the nitronate form, and an iron(IV)-oxo species abstracts proS-H from C4 to initiate intramolecular C-C bond formation. Additionally, the study discovered new homologues that generate cis-configured Ncpa products with different stereochemistries, and identified the critical amino acid residues controlling the stereoselectivity of cyclopropanation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Vasily A. Aleshin, Anastasia V. Graf, Artem V. Artiukhov, Alexander L. Ksenofontov, Lev G. Zavileyskiy, Maria V. Maslova, Victoria I. Bunik
Summary: Epilepsy is a disease characterized by recurrent seizures. Researchers have found that PTZ kindling increases the severity of seizures, alters post-seizure behavior, and affects amino acid metabolism in the brain. However, vitamins B1 and B6 have been shown to have neuroprotective effects by supporting energy and neurotransmitter metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Ella F. Whittle, Madison Chilian, Ehsan Ghayoor Karimiani, Helga Progri, Daniela Buhas, Melis Kose, Rebecca D. Ganetzky, Mehran Beiraghi Toosi, Paria Najarzadeh Torbati, Reza Shervin Badv, Ivan Shelihan, Hui Yang, Houda Zghal Elloumi, Sukyeong Lee, Yalda Jamshidi, Alan M. Pittman, Henry Houlden, Erika Ignatius, Shamima Rahman, Reza Maroofian, Wan Hee Yoon, Christopher J. Carrol
Summary: This study aimed to identify the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities. Through clinical characterization and genetic analysis, the researchers identified three novel homozygous variants in the OGDH gene. Functional studies demonstrated that these variants interfered with the structure and function of the OGDH protein, leading to the observed neurodevelopmental disorder. This research highlights the importance of studying genetic causes of neurodevelopmental disorders for understanding their underlying mechanisms and developing targeted therapies.
GENETICS IN MEDICINE
(2023)
Article
Cell Biology
Wei Xu, Chirag H. Patel, Liang Zhao, Im-Hong Sun, Min-Hee Oh, Im-Meng Sun, Rachel S. Helms, Jiayu Wen, Jonathan D. Powell
Summary: GOT1 plays a crucial role in CD8+ T cell effector differentiation and function by maintaining redox balance and promoting purine nucleotide biosynthesis, glycolytic programming, and cytotoxic function, possibly through posttranslational regulation of HIF protein. Conversely, genetic deletion of GOT1 promotes the generation of memory CD8+ T cells.
Article
Chemistry, Multidisciplinary
Lide Cha, Jared C. Paris, Brady Zanella, Martha Spletzer, Angela Yao, Yisong Guo, Wei-chen Chang
Summary: In this study, in silico methods were used to identify enzymes that have the potential to introduce aziridine rings. Enzymatic activity was reconstituted in vitro to validate the candidates, and it was found that an iron(IV)-oxo species initiates the formation of aziridine rings through C-H bond cleavage. Additionally, the reaction pathway was diverted from aziridination to hydroxylation using mechanistic probes. Isotope tracing experiments and quantitative product analysis provided evidence for the polar capture of a carbocation species by the amine in the pathway to aziridine installation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Oncology
Yong Wang, Jiawen Gao, Shasha Hu, Weiting Zeng, Hongjun Yang, Hui Chen, Shuang Wang
Summary: The study demonstrated that downregulation of SLC25A21 is associated with bladder cancer progression, while overexpression of SLC25A21 inhibits cell proliferation, migration, invasion, and induces apoptosis, ultimately suppressing tumor growth.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiao Liu, Raphael Reinbold, Shuang Liu, Ryan A. Herold, Patrick Rabe, Stephanie Duclos, Rahul B. Yadav, Martine I. Abboud, Sandrine Thieffine, Fraser A. Armstrong, Lennart Brewitz, Christopher J. Schofield
Summary: Variants of isocitrate dehydrogenase (IDH)1/2 alter cancer cell metabolism by reducing 2-oxoglutarate (2OG) to hydroxyglutarate. Synthetic derivatives of 2OG can serve as substrates and 2OG-competitive inhibitors for cancer-associated IDH1/2 variants, and some natural product derivatives are even more efficient substrates than 2OG. The study also suggests the potential of using IDH1/2 variants as biocatalysts and highlights the modulation of IDH1/2 variant activity and inhibition through active site binding.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Gergo Horvath, Gergely Svab, Timea Komlodi, Dora Ravasz, Gergely Kacso, Judit Doczi, Christos Chinopoulos, Attila Ambrus, Laszlo Tretter
Summary: The present study investigates the role of KGDHc and its subunits in the bioenergetics and ROS homeostasis of brain mitochondria. The study reveals that the functioning of KGDHc is associated with decreased oxygen consumption and H2O2 production, as well as attenuated ROS production related to ischemia-reperfusion injury.
Article
Biochemistry & Molecular Biology
Duo Tang, Yuchen Zheng, Guozhen Wang, Chao Sheng, Zijia Liu, Biqi Wang, Qi Zong, Yuchen Zhang, Xiaonan Hou, Mengfei Yao, Zhixiang Zhou
Summary: This study reveals that alpha-ketoglutarate (AKG) can induce cell pyroptosis in esophageal squamous carcinoma cells, while HPV18 E6 inhibits AKG-induced pyroptosis by decreasing P53 expression. The study provides insights into the mechanism of cell pyroptosis induced by high concentrations of AKG and the molecular pathway through which HPV E6 oncoprotein inhibits this process.
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
Biochemical Research Methods
Garik V. Mkrtchyan, Anastasia Graf, Lidia Trofimova, Alexander Ksenofontov, Ludmila Baratova, Victoria Bunik
ANALYTICAL BIOCHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Garik V. Mkrtchyan, Muammer Uecal, Andrea Muellebner, Sergiu Dumitrescu, Martina Kames, Rudolf Moldzio, Marek Molcanyi, Samuel Schaefer, Adelheid Weidinger, Ute Schaefer, Juergen Hescheler, Johanna Catharina Duvigneau, Heinz Redl, Victoria I. Bunik, Andrey V. Kozlov
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2018)
Article
Endocrinology & Metabolism
Anyonya R. Guntur, Akos A. Gerencser, Phuong T. Le, Victoria E. DeMambro, Sheila A. Bornstein, Shona A. Mookerjee, David E. Maridas, David E. Clemmons, Martin D. Brand, Clifford J. Rosen
JOURNAL OF BONE AND MINERAL RESEARCH
(2018)
Article
Biochemistry & Molecular Biology
Hoi-Shan Wong, Berengere Benoit, Martin D. Brand
FREE RADICAL BIOLOGY AND MEDICINE
(2019)
Review
Biochemistry & Molecular Biology
Mark A. Watson, Hoi-Shan Wong, Martin D. Brand
BIOCHEMICAL SOCIETY TRANSACTIONS
(2019)
Article
Biochemistry & Molecular Biology
Jingqi Fang, Hoi-Shan Wong, Martin D. Brand
Review
Biochemistry & Molecular Biology
Shona A. Mookerjee, Akos A. Gerencser, Mark A. Watson, Martin D. Brand
Summary: Mitochondrial oxidation of succinate can generate a higher protonmotive force than that of NADH-linked substrates, due to differences in redox potentials. Biological constraints tune the oxidation of NADH and succinate to maintain suitable mitochondrial pmf for cellular needs without causing pathology. Conditions that allow succinate oxidation to drive pmf too high can lead to pathological generation of reactive oxygen species.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Jingqi Fang, Yini Zhang, Akos A. Gerencser, Martin D. Brand
Summary: The effects of substrate addition on cellular hydrogen peroxide release rate and origin depend on whether endogenous substrates are depleted, and increasing hydrogen peroxide release and improving mitochondrial energy state can enhance the release rate.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Edwin T. Gibbs II, Chad A. Lerner, Mark A. Watson, Hoi-Shan Wong, Akos A. Gerencser, Martin D. Brand
Summary: Superoxide/hydrogen peroxide production by site IQ in complex I occurs during both reverse and forward electron transport, and is equally sensitive to S1QELs, rotenone, and piericidin A. A new assay is introduced to determine the direction of electron flow through complex I. The results show that superoxide/hydrogen peroxide production by site IQ in cells is S1QEL-sensitive and occurs during forward electron transport.
BIOCHEMICAL JOURNAL
(2023)
Article
Endocrinology & Metabolism
David G. Nicholls, Martin D. Brand
Summary: Brown adipose tissue is specialized for thermogenesis, with active mitochondrial electron transport chain and unique uncoupling protein UCP1. Its presence in humans may contribute to diet-induced thermogenesis and protect cardio-metabolic health. Manipulation of creatine metabolism can influence diet- and cold-induced metabolism, but the evidence for a significant futile creatine cycle in these tissues is currently lacking.
Review
Biochemistry & Molecular Biology
Martin D. Brand
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Medicine, General & Internal
Alexandra Boyko, Alexander Ksenofontov, Sergey Ryabov, Lyudmila Baratova, Anastasia Graf, Victoria Bunik
FRONTIERS IN MEDICINE
(2018)
Article
Biochemistry & Molecular Biology
A. L. Ksenofontov, A. I. Boyko, G. V. Mkrtchyan, V. N. Tashlitsky, A. V. Timofeeva, A. V. Graf, V. I. Bunik, L. A. Baratova
BIOCHEMISTRY-MOSCOW
(2017)