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Adenosylcobalamin

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https://www.readbyqxmd.com/read/27858373/vitamin-b12-administration-by-subcutaneous-catheter-device-in-a-cobalamin-a-cbla-patient
#1
E Maines, G Morandi, G Gugelmo, F Ion-Popa, N Campostrini, A Pasini, M Vincenzi, F Teofoli, M Camilot, A Bordugo
Cobalamin A deficiency (cblA) is an inherited disorder of intracellular cobalamin metabolism, caused by impaired 5'-deoxy-adenosylcobalamin (AdoCbl) synthesis. Hydroxocobalamin (OHCbl) is the cornerstone of cblA treatment because vitamin B12 may completely restore AdoCbl deficiency. Parenteral administration, intravenous, subcutaneous or intramuscular, is generally required to achieve effect. Daily injections represent a problem for the parents and the caregivers, and this may lead to poor compliance and scarce adherence to the long-term treatment...
November 18, 2016: JIMD Reports
https://www.readbyqxmd.com/read/27748967/salmonella-enterica-synthesizes-5-6-dimethylbenzimidazolyl-dmb-%C3%AE-riboside-why-some-firmicutes-do-not-require-the-canonical-dmb-activation-system-to-synthesize-adenosylcobalamin
#2
Theodoric A Mattes, Jorge C Escalante-Semerena
5,6-Dimethylbenzimidazolyl-(DMB)-α-ribotide, [α-ribazole-5'-phosphate (α-RP)] is an intermediate in the biosynthesis of adenosylcobalamin (AdoCbl) in many prokaryotes. In such microbes, α-RP is synthesized by nicotinate mononucleotide (NaMN):DMB phosphoribosyltransferases (CobT in S. enterica), in a reaction that is considered to be the canonical step for the activation of the base of the nucleotide present in adenosylcobamides. Some Firmicutes lack CobT-type enzymes, but have a two-protein system comprised of a transporter (i...
October 17, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27693961/molecular-and-cellular-effects-of-vitamin-b12-forms-on-human-trophoblast-cells-in-presence-of-excessive-folate
#3
Tejas Shah, Kalpana Joshi, Sanjay Mishra, Suhas Otiv, Vijay Kumbar
Folic acid (FA) and iron are essential supplements during pregnancy. Similarly effects of vitamin B12 (B12) inadequacy and high folate and low B12 status, on pregnancy outcome are available. However there are no mandatory recommendations for B12. There are many forms of B12 viz. Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl), and Hydroxycobalamin (HCbl) though there is limited consensus on which form has better efficacy. In the present study we have determined effect of various forms of B12 in the presence of two FA concentrations namely normal physiological (20ng/mL; NPFA) and supra-physiological (2000ng/mL; SPFA) concentration to mimic real time situation where FA is in excess due to supplementation...
September 28, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27383231/resonance-raman-spectroscopic-study-of-the-interaction-between-co-ii-rrinoids-and-the-atp-corrinoid-adenosyltransferase-pduo-from-lactobacillus-reuteri
#4
Kiyoung Park, Paola E Mera, Jorge C Escalante-Semerena, Thomas C Brunold
The human-type ATP:corrinoid adenosyltransferase PduO from Lactobacillus reuteri (LrPduO) catalyzes the adenosylation of Co(II)rrinoids to generate adenosylcobalamin (AdoCbl) or adenosylcobinamide (AdoCbi(+)). This process requires the formation of "supernucleophilic" Co(I)rrinoid intermediates in the enzyme active site which are properly positioned to abstract the adeonsyl moiety from co-substrate ATP. Previous magnetic circular dichroism (MCD) spectroscopic and X-ray crystallographic analyses revealed that LrPduO achieves the thermodynamically challenging reduction of Co(II)rrinoids by displacing the axial ligand with a non-coordinating phenylalanine residue to produce a four-coordinate species...
September 2016: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/27356617/mechanism-of-co-c-photodissociation-in-adenosylcobalamin
#5
Brady D Garabato, Piotr Lodowski, Maria Jaworska, Pawel M Kozlowski
A mechanism of Co-C bond photodissociation in the base-on form of adenosylcobalamin (AdoCbl) was investigated by time-dependent density functional theory (TD-DFT). The key mechanistic step involves singlet radical pair (RP) generation from the first electronically excited state (S1). To connect TD-DFT calculations with ultra-fast excited state dynamics, the potential energy surface (PES) of the S1 state was constructed using Co-C and Co-NIm axial coordinates. The S1 PES can be characterized by two minima separated by a seam resulting from the crossing of two surfaces, of metal-to-ligand charge transfer (MLCT) character near the minimum, and a shallow ligand field (LF) surface at elongated axial bond distances...
July 28, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27349184/inborn-error-of-cobalamin-metabolism-associated-with-the-intracellular-accumulation-of-transcobalamin-bound-cobalamin-and-mutations-in-znf143-which-codes-for-a-transcriptional-activator
#6
Mihaela Pupavac, David Watkins, Francis Petrella, Somayyeh Fahiminiya, Alexandre Janer, Warren Cheung, Anne-Claude Gingras, Tomi Pastinen, Joseph Muenzer, Jacek Majewski, Eric A Shoubridge, David S Rosenblatt
Vitamin B12 (cobalamin, Cbl) cofactors adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl) are required for the activity of the enzymes methylmalonyl-CoA mutase (MCM) and methionine synthase (MS). Inborn errors of Cbl metabolism are rare Mendelian disorders associated with hematological and neurological manifestations, and elevations of methylmalonic acid and/or homocysteine in the blood and urine. We describe a patient whose fibroblasts had decreased functional activity of MCM and MS and decreased synthesis of AdoCbl and MeCbl (3...
September 2016: Human Mutation
https://www.readbyqxmd.com/read/27274708/the-proteome-and-lipidome-of-thermococcus-kodakarensis-across-the-stationary-phase
#7
Emma J Gagen, Marcos Y Yoshinaga, Franka Garcia Prado, Kai-Uwe Hinrichs, Michael Thomm
The majority of cells in nature probably exist in a stationary-phase-like state, due to nutrient limitation in most environments. Studies on bacteria and yeast reveal morphological and physiological changes throughout the stationary phase, which lead to an increased ability to survive prolonged nutrient limitation. However, there is little information on archaeal stationary phase responses. We investigated protein- and lipid-level changes in Thermococcus kodakarensis with extended time in the stationary phase...
2016: Archaea: An International Microbiological Journal
https://www.readbyqxmd.com/read/27169753/laboratory-assessment-of-vitamin-b12-status
#8
Dominic J Harrington
The detection and correction of vitamin B12 (B12) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B12 status is commonly estimated using the abundance of the vitamin in serum, with ∼148 pmol/L (200 ng/L) typically set as the threshold for diagnosing deficiency. Serum B12 assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B12 It is only holotranscobalamin that is taken up by cells to meet metabolic demand...
May 11, 2016: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/27072298/fermentative-production-of-1-propanol-from-d-glucose-l-rhamnose-and-glycerol-using-recombinant-escherichia-coli
#9
Mitsuru Matsubara, Nobuyuki Urano, Shohei Yamada, Ai Narutaki, Misaki Fujii, Michihiko Kataoka
Fermentative production of 1-propanol, which is one of the promising precursors of polypropylene production, from d-glucose, l-rhamnose and glycerol using metabolically engineered Escherichia coli was examined. To confer the ability to produce 1-propanol from 1,2-propanediol (1,2-PD) in recombinant E. coli, a part of the pdu regulon including the diol dehydratase and the propanol dehydrogenase genes together with the adenosylcobalamin (AdoCbl) regeneration enzyme genes of Klebsiella pneumoniae was cloned, and an expression vector for these genes (pRSF_pduCDEGHOQS) was constructed...
October 2016: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/27057274/neuregulin-1-promotes-glutathione-dependent-neuronal-cobalamin-metabolism-by-stimulating-cysteine-uptake
#10
Yiting Zhang, Nathaniel Hodgson, Malav Trivedi, Richard Deth
Neuregulin 1 (NRG-1) is a key neurotrophic factor involved in energy homeostasis and CNS development, and impaired NRG-1 signaling is associated with neurological disorders. Cobalamin (Cbl), also known as vitamin B12, is an essential micronutrient which mammals must acquire through diet, and neurologic dysfunction is a primary clinical manifestation of Cbl deficiency. Here we show that NRG-1 stimulates synthesis of the two bioactive Cbl species adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl) in human neuroblastoma cells by both promoting conversion of inactive to active Cbl species and increasing neuronal Cbl uptake...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/26886077/spectroscopic-studies-of-the-eutt-adenosyltransferase-from-salmonella-enterica-mechanism-of-four-coordinate-co-ii-cbl-formation
#11
Ivan G Pallares, Theodore C Moore, Jorge C Escalante-Semerena, Thomas C Brunold
EutT from Salmonella enterica is a member of a class of enzymes termed ATP:Co(I)rrinoid adenosyltransferases (ACATs), implicated in the biosynthesis of adenosylcobalamin (AdoCbl). In the presence of cosubstrate ATP, ACATs raise the Co(II)/Co(I) reduction potential of their cob(II)alamin [Co(II)Cbl] substrate by >250 mV via the formation of a unique four-coordinate (4c) Co(II)Cbl species, thereby facilitating the formation of a "supernucleophilic" cob(I)alamin intermediate required for the formation of the AdoCbl product...
March 23, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/26865262/photolytic-properties-of-cobalamins-a-theoretical-perspective
#12
Pawel M Kozlowski, Brady D Garabato, Piotr Lodowski, Maria Jaworska
This Perspective Article highlights recent theoretical developments, and summarizes the current understanding of the photolytic properties of cobalamins from a computational point of view. The primary focus is on two alkyl cobalamins, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), as well as two non-alkyl cobalamins, cyanocobalamin (CNCbl) and hydroxocobalamin (HOCbl). Photolysis of alkyl cobalamins involves low-lying singlet excited states where photodissociation of the Co-C bond leads to formation of singlet-born alkyl/cob(ii)alamin radical pairs (RPs)...
March 21, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/26799654/decreased-brain-levels-of-vitamin-b12-in-aging-autism-and-schizophrenia
#13
Yiting Zhang, Nathaniel W Hodgson, Malav S Trivedi, Hamid M Abdolmaleky, Margot Fournier, Michel Cuenod, Kim Quang Do, Richard C Deth
Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects...
2016: PloS One
https://www.readbyqxmd.com/read/26788012/characterization-of-vitamin-b12-in-dunaliella-salina
#14
Anantharajappa Kumudha, Ravi Sarada
Vitamin B12 is one of nature's complex metabolite which is industrially produced using certain bacteria. Algae could be an alternative source of vitamin B12 and in this study, vitamin B12 from a halotolerant green alga, Dunaliella salina V-101 was purified and characterized. The extract of Dunaliella was purified by passing through Amberlite XAD-2 and EASI-extract vitamin B12 immunoaffinity column. The total vitamin B12 content in purified sample fractions was 42 ± 2 μg/100 g dry weight as determined by the chemiluminescence method which was almost close to 49 ± 2 μg/100 g dry weight as estimated by microbiological method...
January 2016: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/26704729/diol-dehydratase-reactivase-is-essential-for-recycling-of-coenzyme-b12-in-diol-dehydratase
#15
Tetsuo Toraya, Aya Tanokuchi, Ai Yamasaki, Takehiro Nakamura, Kenichi Ogura, Takamasa Tobimatsu
Holoenzymes of adenosylcobalamin-dependent diol and glycerol dehydratases undergo mechanism-based inactivation by glycerol and O2 inactivation in the absence of substrate, which accompanies irreversible cleavage of the coenzyme Co-C bond. The inactivated holodiol dehydratase and the inactive enzyme·cyanocobalamin complex were (re)activated by incubation with NADH, ATP, and Mg(2+) (or Mn(2+)) in crude extracts of Klebsiella oxytoca, suggesting the presence of a reactivating system in the extract. The reducing system with NADH could be replaced by FMNH2...
January 12, 2016: Biochemistry
https://www.readbyqxmd.com/read/26615597/spectrum-of-mutations-in-60-saudi-patients-with-mut-methylmalonic-acidemia
#16
Faiqa Imtiaz, Bashayer M Al-Mubarak, Abeer Al-Mostafa, Mohamed Al-Hamed, Rabab Allam, Zuhair Al-Hassnan, Mohammed Al-Owain, Hamad Al-Zaidan, Zuhair Rahbeeni, Alya Qari, Eissa Ali Faqeih, Ali Alasmari, Fuad Al-Mutairi, Majid Alfadhel, Wafaa M Eyaid, Mohamed S Rashed, Moeenaldeen Al-Sayed
Defects in the human gene encoding methylmalonyl-CoA mutase enzyme (MCM) give rise to a rare autosomal recessive inherited disorder of propionate metabolism termed mut methylmalonic acidemia (MMA). Patients with mut MMA have been divided into two subgroups: mut(0) with complete loss of MCM activity and mut(-) with residual activity in the presence of adenosylcobalamin (AdoCbl). The disease typically presents in the first weeks or months of life and is clinically characterized by recurrent vomiting, metabolic acidosis, hyperammonemia, lethargy, poor feeding, failure to thrive and neurological deficit...
November 29, 2015: JIMD Reports
https://www.readbyqxmd.com/read/26478482/resolution-and-characterization-of-chemical-steps-in-enzyme-catalytic-sequences-by-using-low-temperature-and-time-resolved-full-spectrum-epr-spectroscopy-in-fluid-cryosolvent-and-frozen-solution-systems
#17
Miao Wang, Chen Zhu, Meghan Kohne, Kurt Warncke
Approaches to the resolution and characterization of individual chemical steps in enzyme catalytic sequences, by using temperatures in the cryogenic range of 190-250 K, and kinetics measured by time-resolved, full-spectrum electron paramagnetic resonance spectroscopy in fluid cryosolvent and frozen solution systems, are described. The preparation and performance of the adenosylcobalamin-dependent ethanolamine ammonia-lyase enzyme from Salmonella typhimurium in the two systems exemplifies the biochemical and spectroscopic methods...
2015: Methods in Enzymology
https://www.readbyqxmd.com/read/26464686/genetic-analysis-of-four-cases-of-methylmalonic-aciduria-and-homocystinuria-cblc-type
#18
Jun Wang, Erzhen Li, Liwen Wang, Zhilong Wang, Shenghai Yang, Qiao Zhou, Qian Chen
Methylmalonic aciduria and homocystinuria, cblC type, is the most common disorder of intracellular vitamin B12 (cobalamin, cbl) metabolism, which results in impaired biosynthesis of methylcobalamin and adenosylcobalamin. The gene MMACHC responsible for the cblC type had been identified, which enables molecular diagnostics. Here, we report four cblC type cases, which were identified by the typical manifestations, and a new approach of next-generation sequencing platform in pediatrics for genetic diseases, further confirmed by Sanger sequencing of the whole MMACHC gene...
2015: International Journal of Clinical and Experimental Pathology
https://www.readbyqxmd.com/read/26443728/biosynthesis-and-use-of-cobalamin-b12
#19
Jorge C Escalante-Semerena, Martin J Warren
This review summarizes research performed over the last 23 years on the genetics, enzyme structures and functions, and regulation of the expression of the genes encoding functions involved in adenosylcobalamin (AdoCbl, or coenzyme B12) biosynthesis. It also discusses the role of coenzyme B12 in the physiology of Salmonella enterica serovar Typhimurium LT2 and Escherichia coli. John Roth's seminal contributions to the field of coenzyme B12 biosynthesis research brought the power of classical and molecular genetic, biochemical, and structural approaches to bear on the extremely challenging problem of dissecting the steps of what has turned out to be one of the most complex biosynthetic pathways known...
September 2008: EcoSal Plus
https://www.readbyqxmd.com/read/26416754/structural-basis-for-gene-regulation-by-a-b12-dependent-photoreceptor
#20
Marco Jost, Jésus Fernández-Zapata, María Carmen Polanco, Juan Manuel Ortiz-Guerrero, Percival Yang-Ting Chen, Gyunghoon Kang, S Padmanabhan, Montserrat Elías-Arnanz, Catherine L Drennan
Photoreceptor proteins enable organisms to sense and respond to light. The newly discovered CarH-type photoreceptors use a vitamin B12 derivative, adenosylcobalamin, as the light-sensing chromophore to mediate light-dependent gene regulation. Here we present crystal structures of Thermus thermophilus CarH in all three relevant states: in the dark, both free and bound to operator DNA, and after light exposure. These structures provide visualizations of how adenosylcobalamin mediates CarH tetramer formation in the dark, how this tetramer binds to the promoter -35 element to repress transcription, and how light exposure leads to a large-scale conformational change that activates transcription...
October 22, 2015: Nature
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