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https://www.readbyqxmd.com/read/28432454/cobalt-tetradehydrocorrins-coordinated-by-imidazolate-like-histidine-in-the-heme-pocket-of-horseradish-peroxidase
#1
Koji Oohora, Ning Tang, Yoshitsugu Morita, Takashi Hayashi
Horseradish peroxidase was reconstituted with cobalt tetradehydrocorrin, rHRP(Co(TDHC)), as a structural analog of cobalamin coordinated with an imidazolate-like His residue, which is generally seen in native enzymes. In contrast to the previously reported cobalt tetradehydrocorrin-reconstituted myoglobin, rMb(Co(TDHC)), the HRP matrix was expected to provide strong axial ligation by His170 which has imidazolate character. rHRP(Co(II)(TDHC)) was characterized by EPR and its reaction with reductants indicates a negative shift of its redox potential compared to rMb(Co(TDHC))...
April 21, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28424758/redox-related-epigenetic-mechanisms-in-glioblastoma-nuclear-factor-erythroid-derived-2-like-2-cobalamin-and-dopamine-receptor-subtype-4
#2
Matthew Scott Schrier, Malav Suchin Trivedi, Richard Carlton Deth
Glioblastoma is an exceptionally difficult cancer to treat. Cancer is universally marked by epigenetic changes, which play key roles in sustaining a malignant phenotype, in addition to disease progression and patient survival. Studies have shown strong links between the cellular redox state and epigenetics. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription factor that upregulates endogenous antioxidant production, and is aberrantly expressed in many cancers, including glioblastoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28416508/hus-and-atypical-hus
#3
T Sakari Jokiranta
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia, and acute kidney failure. HUS is usually categorized as typical, caused by shiga-toxin producing E. coli (STEC) infection, atypical HUS (aHUS), usually caused by uncontrolled complement activation, or secondary HUS with a coexisting disease. In recent years, a general understanding of the pathogenetic mechanisms driving HUS has increased. Typical (i.e. STEC-HUS) follows a gastrointestinal infection with STEC, while aHUS is associated primarily with mutations or autoantibodies leading to dysregulated complement activation...
April 17, 2017: Blood
https://www.readbyqxmd.com/read/28406776/gastric-intestinal-metaplasia-an-intermediate-precancerous-lesion-in-the-cascade-of-gastric-carcinogenesis
#4
Tayyab Hamid Malik, Mujtaba Yousef Al Sayahan, Hussain Ali Al Ahmed, Xu Hong
Gastric intestinal metaplasia, an intermediate lesion in the development of intestinal-type gastric cancer, is observed in the milieu of long standing non-atrophic gastritis and atrophic gastritis. Most patients with intestinal metaplasia remain asymptomatic unless cobalamin deficiency occurs secondary to loss of glands (that produce intrinsic factor and acid). Genetic events that predispose to development of gastric intestinal metaplasia remains an enigma. Mechanisms leading to the progression of atrophy to metaplasia still needs to be comprehensively explored...
March 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28390190/systemic-scedosporium-prolificans-infection-in-an-11-month-old-border-collie-with-cobalamin-deficiency-secondary-to-selective-cobalamin-malabsorption-canine-imerslund-gr%C3%A3-sbeck-syndrome
#5
K Erles, A Mugford, D Barfield, T Leeb, P H Kook
An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture...
April 8, 2017: Journal of Small Animal Practice
https://www.readbyqxmd.com/read/28381531/ratios-of-one-carbon-metabolites-are-functional-markers-of-b-vitamin-status-in-a-norwegian-coronary-angiography-screening-cohort
#6
Arve Ulvik, Steinar Hustad, Adrian McCann, Øivind Midttun, Ottar K Nygård, Per M Ueland
Background: Functional (metabolic) markers of B-vitamin status, including plasma total homocysteine (tHcy) for folate and plasma methylmalonic acid (MMA) for vitamin B-12, suffer from moderate sensitivity and poor specificity. Ratios of metabolites belonging to the same pathway may have better performance characteristics.Objective: We evaluated the ratios of tHcy to total cysteine (tCys; Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to tCys to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status represented by a summary score composed of folate, cobalamin, betaine, pyridoxal 5'-phosphate (PLP), and riboflavin concentrations measured in plasma...
April 5, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28379205/possible-involvement-of-hydrosulfide-in-b12-dependent-methyl-group-transfer
#7
John I Toohey
Evidence from several fields of investigation lead to the hypothesis that the sulfur atom is involved in vitamin B12-dependent methyl group transfer. To compile the evidence, it is necessary to briefly review the following fields: methylation, the new field of sulfane sulfur/hydrogen sulfide (S°/H₂S), hydrosulfide derivatives of cobalamins, autoxidation of hydrosulfide radical, radical S-adenosylmethionine methyl transfer (RSMT), and methionine synthase (MS). Then, new reaction mechanisms for B12-dependent methyl group transfer are proposed; the mechanisms are facile and overcome difficulties that existed in previously-accepted mechanisms...
April 5, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28363510/x-linked-cobalamin-disorder-hcfc1-mimicking-nonketotic-hyperglycinemia-with-increased-both-cerebrospinal-fluid-glycine-and-methylmalonic-acid
#8
Emmanuel Scalais, Elise Osterheld, Christiane Weitzel, Linda De Meirleir, Frederic Mataigne, Geert Martens, Tamim H Shaikh, Curtis R Coughlin, Hung-Chun Yu, Michael Swanson, Marisa W Friederich, Gunter Scharer, Daniel Helbling, Jamie Wendt-Andrae, Johan L K Van Hove
BACKGROUND: Autosomal recessive or X-linked inborn errors of intracellular cobalamin metabolism can lead to methylmalonic aciduria and homocystinuria. In neonates, both increased cerebrospinal fluid glycine and cerebrospinal fluid/plasma glycine ratio are biochemical features of nonketotic hyperglycinemia. METHODS: We describe a boy presenting in the neonatal period with hypotonia, tonic, clonic, and later myoclonic seizures, subsequently evolving into refractory epilepsy and severe neurocognitive impairment...
January 7, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28346939/a-b12-dependent-radical-sam-enzyme-involved-in-oxetanocin-a-biosynthesis
#9
Jennifer Bridwell-Rabb, Aoshu Zhong, He G Sun, Catherine L Drennan, Hung-Wen Liu
Oxetanocin A (OXT-A) is a potent antitumour, antiviral and antibacterial compound. Biosynthesis of OXT-A has been linked to a plasmid-borne Bacillus megaterium gene cluster that contains four genes: oxsA, oxsB, oxrA and oxrB. Here we show that both the oxsA and oxsB genes are required for the production of OXT-A. Biochemical analysis of the encoded proteins, a cobalamin (Cbl)-dependent S-adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD-domain phosphohydrolase, OxsA, reveals that OXT-A is derived from a 2'-deoxyadenosine phosphate in an OxsB-catalysed ring contraction reaction initiated by hydrogen atom abstraction from C2'...
April 20, 2017: Nature
https://www.readbyqxmd.com/read/28338684/seven-enzymes-create-extraordinary-molecular-complexity-in-an-uncultivated-bacterium
#10
Michael F Freeman, Maximilian J Helf, Agneya Bhushan, Brandon I Morinaka, Jörn Piel
Uncultivated bacteria represent a massive resource of new enzymes and bioactive metabolites, but such bacteria remain functionally enigmatic. Polytheonamides are potent peptide cytotoxins produced by uncultivated bacteria that exist as symbionts in a marine sponge. Outside glycobiology, polytheonamides represent the most heavily post-translationally modified biomolecules that are derived from amino acids. The biosynthesis of polytheonamides involves up to 50 site-specific modifications to create a membrane-spanning β-helical structure...
April 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28335526/oral-cyanocobalamin-is-effective-in-the-treatment-of-vitamin-b12-deficiency-in-crohn-s-disease
#11
Fernando Gomollón, Carla J Gargallo, Jose Fernando Muñoz, Raquel Vicente, Alberto Lue, Alberto Mir, Marta García-Alvarado, Marta Gracia, Santiago García-López
Cobalamin deficiency is common in patients with Crohn's disease (CD). Intramuscular cobalamin continues to be the standard therapy for the deficiency and maintenance treatment in these patients, although oral route has been demonstrated to be effective in other pathologies with impaired absorption. Our aims were to evaluate the efficacy of oral therapy in the treatment of cobalamin deficiency and in long-term maintenance in patients with Crohn's disease. We performed a multicenter retrospective cohort study that included 94 patients with Crohn's disease and cobalamin deficiency...
March 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28330909/vitamin-b-12-status-in-infancy-is-positively-associated-with-development-and-cognitive-functioning-5-y-later-in-nepalese-children
#12
Ingrid Kvestad, Mari Hysing, Merina Shrestha, Manjeswori Ulak, Andrew L Thorne-Lyman, Sigrun Henjum, Per M Ueland, Øyvind Midttun, Wafaie Fawzi, Ram K Chandyo, Prakash S Shrestha, Tor A Strand
Background: Poor vitamin B-12 (cobalamin) status is widespread in South Asia. Insufficient vitamin B-12 status has been linked to poor neurodevelopment in young children.Objective: We measured the associations between vitamin B-12 status in infancy (2-12 mo) and the development and cognitive functioning in Nepalese children 5 y later.Design: Vitamin B-12 status was assessed in infancy with the use of plasma cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). At 5 y of age, we measured development with the use of the Ages and Stages Questionnaire, 3rd edition (ASQ-3), and cognitive functioning by using the Developmental Neuropsychological Assessment, 2nd edition (NEPSY II), in 320 children...
March 22, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28329820/hepatocellular-toxicity-of-imidazole-and-triazole-antimycotic-agents
#13
Patrizia Haegler, Lorenz Joerin, Stephan Krähenbühl, Jamal Bouitbir
Hepatotoxicity has been described for all antimycotic azoles currently marketed. A possible mechanism involving mitochondrial dysfunction has been postulated for ketoconazole, but not for the other azoles. The aim of the current investigations was to study the toxicity of different azoles in human cell models and to find out mechanisms of their toxicity. In HepG2 cells, posaconazole and ketoconazole were cytotoxic starting at 20 and 50 µM and decreased the cellular ATP content starting at 5 and 10 µM, respectively...
January 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28327992/cyst-fluid-from-cystic-malignant-brain-tumors-a-reservoir-of-nutrients-including-growth-factor-like-nutrients-for-tumor-cells
#14
Daniel Dahlberg, Eduard A Struys, Erwin E Jansen, Lars Mørkrid, Øivind Midttun, Bjørnar Hassel
BACKGROUND: Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth. OBJECTIVE: To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors. METHODS: Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors. RESULTS: GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3...
January 25, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28325764/the-vitamin-b12-dependent-photoreceptor-aerr-relieves-photosystem-gene-repression-by-extending-the-interaction-of-crtj-with-photosystem-promoters
#15
Mingxu Fang, Carl E Bauer
Purple nonsulfur bacteria adapt their physiology to a wide variety of environmental conditions often through the control of transcription. One of the main transcription factors involved in controlling expression of the Rhodobacter capsulatus photosystem is CrtJ, which functions as an aerobic repressor of photosystem genes. Recently, we reported that a vitamin B12 binding antirepressor of CrtJ called AerR is required for anaerobic expression of the photosystem. However, the mechanism whereby AerR regulates CrtJ activity is unclear...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28325140/vitamins-in-heart-failure-friend-or-enemy
#16
George Georgiopoulos, Christina Chrysohoou, Georgia Vogiatzi, Nikolaos Magkas, Ippokratis Bournelis, Sofia Bampali, Damien Gruson, Dimitris Tousoulis
BACKGROUND: The failing heart is characterized by a depleted metabolic energy reserve and the up-regulation of several molecular mechanisms leading to cardiac hypertrophy, inflammation, fibrosis, angiogenesis, and apoptosis. Dietary or non-dietary supplementation of vitamins could potentially benefit energy balance. OBJECTIVE: The objective of the present study was to evaluate all available information on vitamins supplementation in patients with chronic HF for possible beneficial effect on metabolic, inotropic, chronotropic and hemodynamic indices...
March 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28319307/green-light-induced-inactivation-of-receptor-signaling-using-cobalamin-binding-domains
#17
Stephanie Kainrath, Manuela Stadler, Eva Reichhart, Martin Distel, Harald Janovjak
Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination...
March 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28301169/conformational-dynamics-of-cyanocobalamin-and-its-conjugates-with-peptide-nucleic-acids
#18
Tomasz Pieńko, Aleksandra J Wierzba, Monika Wojciechowska, Dorota Gryko, Joanna Trylska
Vitamin B12 also called cobalamin (Cbl) is an important enzymatic cofactor taken up by mammalian and also by many bacterial cells. Peptide nucleic acid (PNA) is a synthetic DNA analogue that has the ability to bind in a complementary manner to natural nucleic acids. Provided that PNA is efficiently delivered to cells, it could act as a steric blocker of functional DNA or RNA and regulate gene expression at the level of transcription or translation. Recently, Cbl has been examined as a transporter of various molecules to cells...
March 29, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28283521/an-amoebal-grazer-of-cyanobacteria-requires-cobalamin-produced-by-heterotrophic-bacteria
#19
Amy T Ma, Joris Beld, Bianca Brahamsha
Amoebae are unicellular eukaryotes that consume microbial prey through phagocytosis, playing a role in shaping microbial foodwebs. Many amoebal species can be cultivated axenically in rich media or monoxenically with single bacterial prey species. Here we characterize heterolobosean amoeba LPG3, a recent natural isolate, which is unable to grow on unicellular cyanobacteria, its primary food source, in the absence of a heterotrophic bacterium, a Pseudomonas species coisolate. To investigate the molecular basis of this requirement for heterotrophic bacteria, we performed a screen using a defined non-redundant transposon library of Vibrio cholerae which implicated genes in corrinoid uptake and biosynthesis...
March 10, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28265287/pernicious-anemia-associated-cobalamin-deficiency-and-thrombotic-microangiopathy-case-report-and-review-of-the-literature
#20
Farhanah Yousaf, Bruce Spinowitz, Chaim Charytan, Marilyn Galler
A 43-year-old Hispanic male without significant previous medical history was brought to emergency department for syncope following a blood draw to investigate a 40 lbs weight loss during the past 6 months associated with decreased appetite and progressive fatigue. The patient also reported a 1-month history of jaundice. On examination, he was hemodynamically stable and afebrile with pallor and diffuse jaundice but without skin rash or palpable purpura. Normal sensations and power in all extremities were evident on neurological exam...
2017: Case Reports in Medicine
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