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Frontiers in Bioscience (Scholar... Jan 2013Alzheimer's disease (AD) is the most common form of dementia with a progressive course. AD pathology is a manifestation of the underlying severity and neuroanatomic... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia with a progressive course. AD pathology is a manifestation of the underlying severity and neuroanatomic involvement of specific vulnerable brain regions and circuits that are responsible for neuronal dysfunction and death. The etiology of AD is largely unknown. It has been hypothesized that multiple factors, including genetic components, oxidative stress, intracellular or extracellular accumulation of amyloid, dysfunction of cystoskeletal and synapse components, neuronal loss by apoptosis, neuronal excitotoxicity, inflammation, mitochondria dysfunction, etc., may play important roles in the onset of the disease. WWOX/WOX1 is a candidate tumor suppressor. Human WWOX gene, encoding the WW domain-containing oxidoreductase (designated WWOX, FOR, or WOX1) protein, has been mapped to a fragile site on the chromosome ch16q23.3-24.1. Functionally, the WW domain is not only a tumor suppressor, but also a participant in molecular interactions, signaling, and apoptosis in many diseases. In this article, we review the potential mechanism by which WWOX/WOX1 may participate in the pathogenesis of AD with a focus on cell death signaling pathways in neurons.
Topics: Alzheimer Disease; Animals; Cell Death; Humans; Oxidoreductases; Signal Transduction; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase
PubMed: 23277037
DOI: 10.2741/s358 -
Molecules (Basel, Switzerland) Jun 2019In the last decade, new types of solvents called deep eutectic solvents (DES) have been synthesized and commercialized. Among their main advantages, they can be... (Review)
Review
In the last decade, new types of solvents called deep eutectic solvents (DES) have been synthesized and commercialized. Among their main advantages, they can be eco-friendly and are easy to synthesize at different molar ratios depending on the desired solvent properties. This review aims to show the different uses of DES in some relevant biocatalytic redox reactions. Here we analyze oxidoreductase-mediated transformations that are performed in the presence of DES and compare them with the ones that avoided those solvents. DES were found to present advantages such as the increase in the product yield and enantiomeric excess in many reactions.
Topics: Animals; Aquatic Organisms; Bacteria; Biocatalysis; Biotechnology; Catalase; Humans; Oxidation-Reduction; Oxidoreductases; Plants; Solvents
PubMed: 31212686
DOI: 10.3390/molecules24112190 -
Frontiers in Bioscience (Elite Edition) Jan 2012Alzheimer's disease (AD) is the most common form of dementia with a progressive course. AD pathology is a manifestation of the underlying severity and neuroanatomic... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia with a progressive course. AD pathology is a manifestation of the underlying severity and neuroanatomic involvement of specific vulnerable brain regions and circuits that are responsible for neuronal dysfunction and death. The etiology of AD is largely unknown. It has been hypothesized that multiple factors, including genetic components, oxidative stress, intracellular or extracellular accumulation of amyloid, dysfunction of cystoskeletal and synapse components, neuronal loss by apoptosis, neuronal excitotoxicity, inflammation, mitochondria dysfunction, etc., may play important roles in the onset of the disease. WWOX/WOX1 is a candidate tumor suppressor. Human WWOX gene, encoding the WW domain-containing oxidoreductase (designated WWOX, FOR, or WOX1) protein, has been mapped to a fragile site on the chromosome ch16q23.3-24.1. Functionally, the WW domain is not only a tumor suppressor, but also a participant in molecular interactions, signaling, and apoptosis in many diseases. In this article, we review the potential mechanism by which WWOX/WOX1 may participate in the pathogenesis of AD with a focus on cell death signaling pathways in neurons.
Topics: Alzheimer Disease; Cell Death; Humans; Oxidoreductases; Signal Transduction; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase
PubMed: 22202011
DOI: 10.2741/e516 -
Cytogenetic and Genome Research 2016FHIT, located at FRA3B, is one of the most commonly deleted genes in human cancers, and loss of FHIT protein is one of the earliest events in cancer initiation. However,... (Review)
Review
FHIT, located at FRA3B, is one of the most commonly deleted genes in human cancers, and loss of FHIT protein is one of the earliest events in cancer initiation. However, location of FHIT at a chromosomal fragile site, a locus prone to breakage and gap formation under even mild replication stress, has encouraged claims that FHIT loss is a passenger event in cancers. We summarize accumulated evidence that FHIT protein functions as a genome "caretaker" required to protect the stability of genomes of normal cells of most tissues from agents causing intrinsic and extrinsic DNA damage. FHIT loss leads to intracellular replication stress and subsequent genome instability, which provides an opportunistic mutational landscape in preneoplasias for selection of a variety of other cancer-driving mutations. We also review evidence showing that FHIT loss leads to enhanced activation of other common fragile sites, including the FRA16D/WWOX locus, and creates optimal single-stranded DNA substrates for the hypermutator enzyme, APOBEC3B.
Topics: Acid Anhydride Hydrolases; Chromosome Fragile Sites; Genes, p53; Genomic Instability; Humans; Mutation; Neoplasm Proteins; Neoplasms; Oxidoreductases; Precancerous Conditions; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase
PubMed: 28199992
DOI: 10.1159/000455753 -
Plant Physiology and Biochemistry : PPB Jan 2016L-Ascorbic acid (ascorbate, AsA, vitamin C) is essential for animal and plant health. Despite our dependence on fruits and vegetables to fulfill our requirement for this... (Review)
Review
L-Ascorbic acid (ascorbate, AsA, vitamin C) is essential for animal and plant health. Despite our dependence on fruits and vegetables to fulfill our requirement for this vitamin, the metabolic network leading to its formation in plants is just being fully elucidated. There is evidence supporting the operation of at least four biosynthetic pathways leading to AsA formation in plants. These routes use D-mannose/L-galactose, L-gulose, D-galacturonate, and myo-inositol as the main precursors. This review focuses on aldonolactone oxidoreductases, a subgroup of the vanillyl alcohol oxidase (VAO; EC 1.1.3.38) superfamily, enzymes that catalyze the terminal step in AsA biosynthesis in bacteria, protozoa, animals, and plants. In this report, we review the properties of well characterized aldonolactone oxidoreductases to date. A shared feature in these proteins is the presence of a flavin cofactor as well as a thiol group. The flavin cofactor in many cases is bound to the N terminus of the enzymes or to a recently discovered HWXK motif in the C terminus. The binding between the flavin moiety and the protein can be either covalent or non-covalent. Substrate specificity and subcellular localization differ among the isozymes of each kingdom. All oxidases among these enzymes possess dehydrogenase activity, however, exclusive dehydrogenases are also found. We also discuss recent evidence indicating that plants have both L-gulono-1,4-lactone oxidases and L-galactono-1,4-lactone dehydrogenases involved in AsA biosynthesis.
Topics: Alcohol Oxidoreductases; Amino Acid Sequence; Ascorbic Acid; Coenzymes; Flavins; Galactose; Lactones; Mannose; Molecular Sequence Data; Oxidation-Reduction; Oxidoreductases; Plants; Recombinant Proteins; Sequence Alignment; Substrate Specificity; Sugar Acids
PubMed: 26696130
DOI: 10.1016/j.plaphy.2015.11.017 -
Protein Science : a Publication of the... Apr 2016The Gfo/Idh/MocA protein family contains a number of different proteins, which almost exclusively consist of NAD(P)-dependent oxidoreductases that have a diverse set of... (Review)
Review
The Gfo/Idh/MocA protein family contains a number of different proteins, which almost exclusively consist of NAD(P)-dependent oxidoreductases that have a diverse set of substrates, typically pyranoses. In this study, to clarify common structural features that would contribute to their function, the available crystal structures of the members of this family have been analyzed. Despite a very low sequence identity, the central features of the three-dimensional structures of the proteins are surprisingly similar. The members of the protein family have a two-domain structure consisting of a N-terminal nucleotide-binding domain and a C-terminal α/β-domain. The C-terminal domain contributes to the substrate binding and catalysis, and contains a βα-motif with a central α-helix carrying common essential amino acid residues. The β-sheet of the α/β-domain contributes to the oligomerization in most of the proteins in the family.
Topics: Binding Sites; Catalysis; Catalytic Domain; Crystallography, X-Ray; Models, Molecular; Multigene Family; Oxidoreductases; Protein Multimerization; Protein Structure, Secondary
PubMed: 26749496
DOI: 10.1002/pro.2877 -
Orphanet Journal of Rare Diseases Oct 2021Biallelic variants in HSD3B7 cause 3β-hydroxy-Δ-C-steroid oxidoreductase (HSD3B7) deficiency, a life-threatening but treatable liver disease. The goal of this study...
BACKGROUND
Biallelic variants in HSD3B7 cause 3β-hydroxy-Δ-C-steroid oxidoreductase (HSD3B7) deficiency, a life-threatening but treatable liver disease. The goal of this study was to obtain detailed information on the correlation between the genotype and phenotype of HSD3B7 deficiency and to report on responses to primary bile acid therapy.
METHODS
The medical records of a cohort of 39 unrelated patients with genetically and biochemically confirmed HSD3B7 deficiency were examined to determine whether there exist genotype-phenotype relationships in this bile acid synthesis disorder.
RESULTS
In all, 34 of the 44 variants identified in HSD3B7 were novel. A total of 32 patients presented early with neonatal cholestasis, and 7 presented after 1-year of age with liver failure (n = 1), liver cirrhosis (n = 3), cholestasis (n = 1), renal cysts and abnormal liver biochemistries (n = 1), and coagulopathy from vitamin K1 deficiency and abnormal liver biochemistries (n = 1). Renal lesions, including renal cysts, renal stones, calcium deposition and renal enlargement were observed in 10 of 35 patients. Thirty-three patients were treated with oral chenodeoxycholic acid (CDCA) resulting in normalization of liver biochemistries in 24, while 2 showed a significant clinical improvement, and 7 underwent liver transplantation or died. Remarkably, renal lesions in 6 patients resolved after CDCA treatment, or liver transplantation. There were no significant correlations between genotype and clinical outcomes.
CONCLUSIONS
In what is the largest cohort of patients with HSD3B7 deficiency thus far studied, renal lesions were a notable clinical feature of HSD3B7 deficiency and these were resolved with suppression of atypical bile acids by oral CDCA administration.
Topics: 3-Hydroxysteroid Dehydrogenases; Bile Acids and Salts; China; Cholestasis; Humans; Infant, Newborn; Oxidoreductases
PubMed: 34627351
DOI: 10.1186/s13023-021-02041-7 -
Analytical Sciences : the International... Oct 2008Due to their unique characteristics ionic liquids (ILs) have been extensively used as solvents in enzymatic procedures, proving to be advantageous alternatives to... (Review)
Review
Due to their unique characteristics ionic liquids (ILs) have been extensively used as solvents in enzymatic procedures, proving to be advantageous alternatives to conventional organic solvents. The studies of enzyme behavior in ILs have increased exponentially in the last years and oxidoreductases particularly have recently started to be studied. The association of oxidoreductases with IL is very promising due to the large field of application of these enzymes. The materials are very interesting not only from the analytical point of view but also in the biocatalytic perspective. In this review, we discuss the behavior of oxidoreductases in the presence of ILs, the mechanisms involved in this association and the immobilization of oxidoreductases in composite materials with IL. The performance of proteins with peroxidase activity in ILs is also reviewed. Future trends and perspectives related with the development of biocatalytic studies involving oxidoreductases and ILs are also considered.
Topics: Animals; Enzymes, Immobilized; Humans; Ionic Liquids; Oxidoreductases; Peroxidase
PubMed: 18845879
DOI: 10.2116/analsci.24.1231 -
The Journal of Biological Chemistry May 2022Oxidation of malate to oxaloacetate, catalyzed by either malate dehydrogenase (Mdh) or malate quinone oxidoreductase (Mqo), is a critical step of the tricarboxylic acid...
Oxidation of malate to oxaloacetate, catalyzed by either malate dehydrogenase (Mdh) or malate quinone oxidoreductase (Mqo), is a critical step of the tricarboxylic acid cycle. Both Mqo and Mdh are found in most bacterial genomes, but the level of functional redundancy between these enzymes remains unclear. A bioinformatic survey revealed that Mqo was not as widespread as Mdh in bacteria but that it was highly conserved in mycobacteria. We therefore used mycobacteria as a model genera to study the functional role(s) of Mqo and its redundancy with Mdh. We deleted mqo from the environmental saprophyte Mycobacterium smegmatis, which lacks Mdh, and found that Mqo was essential for growth on nonfermentable carbon sources. On fermentable carbon sources, the Δmqo mutant exhibited delayed growth and lowered oxygen consumption and secreted malate and fumarate as terminal end products. Furthermore, heterologous expression of Mdh from the pathogenic species Mycobacterium tuberculosis shortened the delayed growth on fermentable carbon sources and restored growth on nonfermentable carbon sources at a reduced growth rate. In M. tuberculosis, CRISPR interference of either mdh or mqo expression resulted in a slower growth rate compared to controls, which was further inhibited when both genes were knocked down simultaneously. These data reveal that exergonic Mqo activity powers mycobacterial growth under nonenergy limiting conditions and that endergonic Mdh activity complements Mqo activity, but at an energetic cost for mycobacterial growth. We propose Mdh is maintained in slow-growing mycobacterial pathogens for use under conditions such as hypoxia that require reductive tricarboxylic acid cycle activity.
Topics: Bacterial Proteins; Carbon; Citric Acid Cycle; Malate Dehydrogenase; Malates; Mycobacterium smegmatis; Oxaloacetic Acid; Oxidoreductases
PubMed: 35337802
DOI: 10.1016/j.jbc.2022.101859 -
Molekuliarnaia Biologiia 2013There are no doubt about the important role of free radicals and reactive oxygen species in the processes of cell activity. The disturbances of intracellular redox... (Review)
Review
There are no doubt about the important role of free radicals and reactive oxygen species in the processes of cell activity. The disturbances of intracellular redox processes are often accompanied with the development of such common pathologies as diabetes, myocardial infarction, neurodegeneration, broncho-pulmonary diseases, cancer, etc. To date, there are a large number of antioxidant enzymes related to different redox biology systems, the key role among them is played by enzymes belong to the thiol oxidoreductases superfamily, which consists of thioredoxin, glutaredoxin, peroxiredoxin, protein disulfidizomeraz, glutathione peroxidase families, and a number of other proteins. In addition to the antioxidant function, thiol oxidoreductases display the ability to recycle of hydroperoxide to form specific disulfide bonds within and between proteins that significantly extends the range of their functionality. Therefore, biochemical characterization and elucidation of functional mechanisms of the superfamily proteins is a highly actual problem of redox biology.
Topics: Glutaredoxins; Glutathione Peroxidase; Hydrogen Peroxide; Oxidoreductases; Peroxiredoxins; Sulfhydryl Compounds; Thioredoxins
PubMed: 24466746
DOI: 10.7868/s0026898413040149