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Ferroptosis as a target for protection against cardiomyopathy Open
Significance Nonapoptotic cell death-induced tissue damage has been implicated in a variety of diseases, including neurodegenerative disorder, inflammation, and stroke. In this study, we demonstrate that ferroptosis, a newly defined iron-d…
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Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects Open
Regulatory and functional aspects of the kynurenine (K) pathway (KP) of tryptophan (Trp) degradation are reviewed. The KP accounts for ~95% of dietary Trp degradation, of which 90% is attributed to the hepatic KP. During immune activation,…
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Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins Open
As a result of the adaptation of life to an aerobic environment, nature has evolved a panoply of metalloproteins for oxidative metabolism and protection against reactive oxygen species. Despite the diverse structures and functions of these…
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The Roles of NRF2 in Modulating Cellular Iron Homeostasis Open
Further studies are necessary to connect NRF2 activation with physiological and pathological changes to iron signaling and oxidative stress. Antioxid. Redox Signal. 00, 000-000.
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Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life Open
Bringing carbon-silicon bonds to life Organic compounds containing silicon are important for a number of applications, from polymers to semiconductors. The catalysts used for creating carbon-silicon bonds, however, often require expensive …
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A Dual Role of Heme Oxygenase-1 in Cancer Cells Open
Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, and it has been suggested to demonstrate cytoprotective effects against various stress-related conditions. HO-1 is commonly reg…
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Mitochondria and Iron: current questions Open
Mitochondria are cellular organelles that perform numerous bioenergetic, biosynthetic, and regulatory functions and play a central role in iron metabolism. Extracellular iron is taken up by cells and transported to the mitochondria, where …
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Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives Open
Myeloperoxidase (MPO) belongs to the family of heme-containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kDa) is the product of the MPO gene located on long arm of chromosome 17. The primary ge…
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Heme and Nonheme High-Valent Iron and Manganese Oxo Cores in Biological and Abiological Oxidation Reactions Open
Utilization of O2 as an abundant and environmentally benign oxidant is of great interest in the design of bioinspired synthetic catalytic oxidation systems. Metalloenzymes activate O2 by employing earth-abundant metals and exhibit diverse …
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Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells Open
Ferroptosis is an iron-dependent form of regulated nonapoptotic cell death, which contributes to damage in models of acute kidney injury (AKI). Heme oxygenase-1 (HO-1) is a cytoprotective enzyme induced in response to cellular stress, and …
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Prokaryotic Heme Biosynthesis: Multiple Pathways to a Common Essential Product Open
SUMMARY The advent of heme during evolution allowed organisms possessing this compound to safely and efficiently carry out a variety of chemical reactions that otherwise were difficult or impossible. While it was long assumed that a single…
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Biomimetic Reactivity of Oxygen-Derived Manganese and Iron Porphyrinoid Complexes Open
Heme proteins utilize the heme cofactor, an iron porphyrin, to perform a diverse range of reactions including dioxygen binding and transport, electron transfer, and oxidation/oxygenations. These reactions share several key metalloporphyrin…
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Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for Selective Carbene and Nitrene Transfer Open
Despite the astonishing diversity of naturally occurring biocatalytic processes, enzymes do not catalyze many of the transformations favored by synthetic chemists. Either nature does not care about the specific products, or if she does, sh…
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Activation of Dioxygen by Iron and Manganese Complexes: A Heme and Nonheme Perspective Open
The rational design of well-defined, first-row transition metal complexes that can activate dioxygen has been a challenging goal for the synthetic inorganic chemist. The activation of O2 is important in part because of its central role in …
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Molecular Mechanisms of Drug Resistance in <i>Plasmodium falciparum</i> Malaria Open
Understanding and controlling the spread of antimalarial resistance, particularly to artemisinin and its partner drugs, is a top priority. Plasmodium falciparum parasites resistant to chloroquine, amodiaquine, or piperaquine harbor mutatio…
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COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism Open
The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory infection caused by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat coronavirus. In this study, conserved domain analys…
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Molecular Mechanisms of Iron and Heme Metabolism Open
An abundant metal in the human body, iron is essential for key biological pathways including oxygen transport, DNA metabolism, and mitochondrial function. Most iron is bound to heme but it can also be incorporated into iron-sulfur clusters…
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Multifunctional Cytochrome <i>c</i>: Learning New Tricks from an Old Dog Open
Cytochrome c (cyt c) is a small soluble heme protein characterized by a relatively flexible structure, particularly in the ferric form, such that it is able to sample a broad conformational space. Depending on the specific conditions, inte…
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Heme Oxygenases in Cardiovascular Health and Disease Open
Heme oxygenases are composed of two isozymes, Hmox1 and Hmox2, that catalyze the degradation of heme to carbon monoxide (CO), ferrous iron, and biliverdin, the latter of which is subsequently converted to bilirubin. While initially conside…
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Enzymatic construction of highly strained carbocycles Open
Double rings made with heme Cyclic organic structures with adjacent three-carbon rings—bicyclobutanes—are useful starting materials for chemical and materials synthesis owing to their extreme ring strain. Constructing these molecules is a …
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Heme Oxygenase-1 Signaling and Redox Homeostasis in Physiopathological Conditions Open
Heme-oxygenase is the enzyme responsible for degradation of endogenous iron protoporphyirin heme; it catalyzes the reaction’s rate-limiting step, resulting in the release of carbon monoxide (CO), ferrous ions, and biliverdin (BV), which is…
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Insight into G-quadruplex-hemin DNAzyme/RNAzyme: adjacent adenine as the intramolecular species for remarkable enhancement of enzymatic activity Open
G-quadruplex (G4) with stacked G-tetrads structure is able to bind hemin (iron (III)-protoporphyrin IX) to form a unique type of DNAzyme/RNAzyme with peroxidase-mimicking activity, which has been widely employed in multidisciplinary fields…
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HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation Open
The upregulation of heme oxygenase-1 (HO-1) is one of the most important mechanisms of cell adaptation to stress. Indeed, the redox sensitive transcription factor Nrf2 is the pivotal regulator of HO-1 induction. Through the antioxidant, an…
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Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders Open
The heme oxygenase (HO) enzyme system catabolizes heme to carbon monoxide (CO), ferrous iron, and biliverdin-IXα (BV), which is reduced to bilirubin-IXα (BR) by biliverdin reductase (BVR). HO activity is represented by two distinct isozyme…
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Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection Open
Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and chronic lung infections in cystic fibrosis patients. Iron is essential for bacterial growth, and P. aeruginosa expresses multiple iron uptake systems, whose role …
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Structure and function of the cytochrome P450 peroxygenase enzymes Open
The cytochromes P450 (P450s or CYPs) constitute a large heme enzyme superfamily, members of which catalyze the oxidative transformation of a wide range of organic substrates, and whose functions are crucial to xenobiotic metabolism and ste…
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Heme Oxygenase-1 and Carbon Monoxide in the Heart Open
Understanding the processes governing the ability of the heart to repair and regenerate after injury is crucial for developing translational medical solutions. New avenues of exploration include cardiac cell therapy and cellular reprogramm…
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Nitric Oxide in Macrophage Immunometabolism: Hiding in Plain Sight Open
Nitric Oxide (NO) is a soluble endogenous gas with various biological functions like signaling, and working as an effector molecule or metabolic regulator. In response to inflammatory signals, immune myeloid cells, like macrophages, increa…
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The Role of Astrocytes in the Central Nervous System Focused on BK Channel and Heme Oxygenase Metabolites: A Review Open
Astrocytes outnumber neurons in the human brain, and they play a key role in numerous functions within the central nervous system (CNS), including glutamate, ion (i.e., Ca2+, K+) and water homeostasis, defense against oxidative/nitrosative…
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Immune-modulating enzyme indoleamine 2,3-dioxygenase is effectively inhibited by targeting its apo-form Open
Significance Indoleamine 2,3-dioxygenase (IDO1) is a heme protein that catalyzes the dioxygenation of tryptophan. Cells expressing this activity are able to profoundly alter their surrounding environment to suppress the immune response. Ca…