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Adenosylcobalamin

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https://www.readbyqxmd.com/read/29741927/transcellular-transport-of-cobalamin-in-aortic-endothelial-cells
#1
Luciana Hannibal, Keerthana Bolisetty, Armend Axhemi, Patricia M DiBello, Edward V Quadros, Sergey Fedosov, Donald W Jacobsen
Cobalamin [Cbl (or B12 )] deficiency causes megaloblastic anemia and a variety of neuropathies. However, homeostatic mechanisms of cyanocobalamin (CNCbl) and other Cbls by vascular endothelial cells are poorly understood. Herein, we describe our investigation into whether cultured bovine aortic endothelial cells (BAECs) perform transcytosis of B12 , namely, the complex formed between serum transcobalamin and B12 , designated as holo-transcobalamin (holo-TC). We show that cultured BAECs endocytose [57 Co]-CNCbl-TC (source material) via the CD320 receptor...
May 9, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29713722/magnetic-field-effects-on-coenzyme-b-12-and-b-6-dependent-lysine-5-6-aminomutase-switching-of-the-j-resonance-through-a-kinetically-competent-radical-pair-intermediate
#2
Jun-Ru Chen, Shyue-Chu Ke
The environmental magnetic field is beneficial to migratory bird navigation through the radical-pair mechanism. One of the continuing challenges in understanding how magnetic fields may perturb biological processes is that only a very few field-sensitive examples have been explored despite the prevalence of radical pairs in enzymatic reactions. We show that the reaction of adenosylcobalamin- and pyridoxal-5'-phosphate-dependent lysine 5,6-aminomutase proceeds via radical-pair intermediates and is magnetic field dependent...
May 1, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29526088/characterization-of-1-2-propanediol-dehydratases-reveals-distinct-mechanisms-for-b-12-dependent-and-glycyl-radical-enzymes
#3
Benjamin J Levin, Emily P Balskus
Propanediol dehydratase (PD), a recently characterized member of the glycyl radical enzyme (GRE) family, uses protein-based radicals to catalyze the chemically challenging dehydration of ( S)-1,2-propanediol. This transformation is also performed by the well-studied enzyme B12 -dependent propanediol dehydratase (B12 -PD) using an adenosylcobalamin cofactor. Despite the prominence of PD in anaerobic microorganisms, it remains unclear if the mechanism of this enzyme is similar to that of B12 -PD. Here we report 18 O labeling experiments that suggest PD and B12 -PD employ distinct mechanisms...
March 16, 2018: Biochemistry
https://www.readbyqxmd.com/read/29211762/ribofacseq-a-new-method-for-investigating-metabolic-and-transport-pathways-in-bacterial-cells-by-combining-a-riboswitch-based-sensor-fluorescence-activated-cell-sorting-and-next-generation-sequencing
#4
Zohaib Ghazi, Shahrzad Jahanshahi, Yingfu Li
The elucidation of the cellular processes involved in vitamin and cofactor biosynthesis is a challenging task. The conventional approaches to these investigations rely on the discovery and purification of the products (i.e proteins and metabolites) of a particular transport or biosynthetic pathway, prior to their subsequent analysis. However, the purification of low-abundance proteins or metabolites is a formidable undertaking that presents considerable technical challenges. As a solution, we present an alternative approach to such studies that circumvents the purification step...
2017: PloS One
https://www.readbyqxmd.com/read/29150289/the-cause-of-multiple-sclerosis-is-autoimmune-attack-of-adenosyltransferase-thereby-limiting-adenosylcobalamin-production
#5
J L Boucher
The pathogenesis of multiple sclerosis (MS) begins with an infection by a bacterium from the class of bacteria that produce and utilize adenosylcobalamin (AdoCbl) and possess an adenosyl transferase enzyme (ATR); these bacteria are the exogenous antigens that cause MS. Human ATR is homologous to bacterial ATR and B cells produce anti-ATR antibodies as an autoimmune response thereby reducing the concentration of ATR and thus limiting production of AdoCbl, one of the two bioactive forms of vitamin B12. The next step in MS pathogenesis is a period of subclinical AdoCbl deficiency over a period of many years resulting in production of odd-carbon-number fatty acids that are incorporated into myelin rendering it antigenic...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29136199/site-specific-dual-color-labeling-of-long-rnas-for-single-molecule-spectroscopy
#6
Meng Zhao, Fabio D Steffen, Richard Börner, Michelle F Schaffer, Roland K O Sigel, Eva Freisinger
Labeling of long RNA molecules in a site-specific yet generally applicable manner is integral to many spectroscopic applications. Here we present a novel covalent labeling approach that is site-specific and scalable to long intricately folded RNAs. In this approach, a custom-designed DNA strand that hybridizes to the RNA guides a reactive group to target a preselected adenine residue. The functionalized nucleotide along with the concomitantly oxidized 3'-terminus can subsequently be conjugated to two different fluorophores via bio-orthogonal chemistry...
February 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29032242/combination-of-vitamin-b12-active-forms-improved-fetal-growth-in-wistar-rats-through-up-regulation-of-placental-mir-16-and-mir-21-levels
#7
Tejas Shah, Sanjay Mishra, Amol More, Suhas Otiv, Kishori Apte, Kalpana Joshi
AIM: Epidemiological studies have indicated importance of folate and vitamin (B12) during pregnancy. Also available evidence on efficacy of B12 forms viz. Cyanocobalamin (Cbl), Methylcobalamin (MeCbl), Adenosylcobalamin (AdCbl) and Hydroxycobalamin (HCbl) in preventing or treating cobalamin deficiency is limited. The present study examines the effect of various forms of B12 in combination with folate during pregnancy and their effect on gestational outcomes. MAIN METHOD: In the present study, we examined the effect of various vitamin B12 forms in presence of recommended folate (RFol: 400μg/day) and high folate (HFol: 5mg/day) on gestational outcomes in female Wistar rats...
December 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28943303/human-mmaa-induces-the-release-of-inactive-cofactor-and-restores-methylmalonyl-coa-mutase-activity-through-their-complex-formation
#8
Toshiko Takahashi-Iñiguez, Alfonso González-Noriega, Colette Michalak, María Elena Flores
Human mitochondrial methylmalonyl-CoA mutase (hMCM) is an isomerase that converts methylmalonyl-CoA to succinyl-CoA, a crucial step for the incorporation of some compounds derived from the diet into the central metabolism. hMCM employs highly reactive radicals from its cofactor (adenosylcobalamin, AdoCbl) to perform its reaction. Our previous work demonstrated that hMCM loses activity during catalysis and that the interaction with human MMAA (hMMAA), a GTPase protein, avoided this loss or restored hMCM activity...
November 2017: Biochimie
https://www.readbyqxmd.com/read/28818601/complete-genome-sequence-of-pseudomonas-antarctica-pamc-27494-a-bacteriocin-producing-psychrophile-isolated-from-antarctica
#9
Jaejin Lee, Yong-Joon Cho, Jae Young Yang, You-Jung Jung, Soon Gyu Hong, Ok-Sun Kim
Antimicrobial-producing, cold-adapted microorganisms have great potential for biotechnological applications in food, pharmaceutical, and cosmetic industries. Pseudomonas antarctica PAMC 27494, a psychrophile exhibiting antimicrobial activity, was isolated from an Antarctic freshwater sample. Here we report the complete genome of P. antarctica PAMC 27494. The strain contains a gene cluster encoding microcin B which inhibits DNA regulations by targeting the DNA gyrase. PAMC 27494 may produce R-type pyocins and also contains a complete set of proteins for the biosynthesis of adenosylcobalamin and possibly induces plant growth by supplying pyrroloquinoline quionone molecules...
August 14, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28634850/novel-vitamin-b-12-producing-enterococcus-spp-and-preliminary-in-vitro-evaluation-of-probiotic-potentials
#10
Ping Li, Qing Gu, Yuejiao Wang, Yue Yu, Lanlan Yang, Jieyan V Chen
Vitamin B12 is an essential nutrient required for crucial metabolic processes in humans. Vitamin B12 -producing lactic acid bacteria (LAB) have been attracting increased attentions currently because of the generally recognized as safe (GRAS) status. Most of recent studies focused on Lactobacillus, and little is known about B12 -producing Enterococcus. In the present study, five Enterococcus strains isolated from infant feces were identified as vitamin B12 producers. Among them, Enterococcus faecium LZ86 had the highest B12 production (499...
August 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28551266/characterization-of-extracellular-vitamin-b12-producing-lactobacillus-plantarum-strains-and-assessment-of-the-probiotic-potentials
#11
Ping Li, Qing Gu, Lanlan Yang, Yue Yu, Yuejiao Wang
We investigated extracellular vitamin B12-producing Lactobacillus strains and their characteristics in tolerance to environmental stresses, gastric acid and bile salts. Two isolates, Lactobacillus plantarum LZ95 and CY2, showed high extracellular B12 production, 98±15μg/L and 60±9μg/L respectively. Extracellular B12 from LZ95 were identified as adenosylcobalamin and methylcobalamin using a combination of solid phase extraction and reverse-phase HPLC, while that from CY2 was adenosylcobalamin. Both strains grew under environmental stresses, and LZ95 exhibited better tolerance to low temperature and high ethanol concentration...
November 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28533376/b-12-dependent-photoresponsive-protein-hydrogels-for-controlled-stem-cell-protein-release
#12
Ri Wang, Zhongguang Yang, Jiren Luo, I-Ming Hsing, Fei Sun
Thanks to the precise control over their structural and functional properties, genetically engineered protein-based hydrogels have emerged as a promising candidate for biomedical applications. Given the growing demand for creating stimuli-responsive "smart" hydrogels, here we show the synthesis of entirely protein-based photoresponsive hydrogels by covalently polymerizing the adenosylcobalamin (AdoB12 )-dependent photoreceptor C-terminal adenosylcobalamin binding domain (CarHC ) proteins using genetically encoded SpyTag-SpyCatcher chemistry under mild physiological conditions...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28528213/optimal-electrostatic-interactions-between-substrate-and-protein-are-essential-for-radical-chemistry-in-ornithine-4-5-aminomutase
#13
Caitlyn Makins, Douglas A Whitelaw, Michael McGregor, Alix Petit, Robert G Mothersole, Kathleen E Prosser, Kirsten R Wolthers
Ornithine 4,5-aminomutase (OAM) from Clostridium sticklandii is an adenosylcobalamin (AdoCbl) and pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes a 1,2-amino shift, interconverting d-ornithine and 2S, 4R-diaminopentanoate. The reaction occurs via a radical-based mechanism whereby a PLP-bound substrate radical undergoes intramolecular isomerization via an azacyclopropylcarbinyl radical intermediate. Herein, we investigated the catalytic role of active site residues that form non-covalent interactions with PLP and/or substrate, d-ornithine...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28497574/protein-destabilization-and-loss-of-protein-protein-interaction-are-fundamental-mechanisms-in-cbla-type-methylmalonic-aciduria
#14
Tanja Plessl, Céline Bürer, Seraina Lutz, Wyatt W Yue, Matthias R Baumgartner, D Sean Froese
Mutations in the human MMAA gene cause the metabolic disorder cblA-type methylmalonic aciduria (MMA), although knowledge of the mechanism of dysfunction remains lacking. MMAA regulates the incorporation of the cofactor adenosylcobalamin (AdoCbl), generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT). This function of MMAA depends on its GTPase activity, which is stimulated by an interaction with MUT. Here, we present 67 new patients with cblA-type MMA, identifying 19 novel mutations...
August 2017: Human Mutation
https://www.readbyqxmd.com/read/28483920/cobalamin-riboswitches-exhibit-a-broad-range-of-ability-to-discriminate-between-methylcobalamin-and-adenosylcobalamin
#15
COMPARATIVE STUDY
Jacob T Polaski, Samantha M Webster, James E Johnson, Robert T Batey
Riboswitches are a widely distributed class of regulatory RNAs in bacteria that modulate gene expression via small-molecule-induced conformational changes. Generally, these RNA elements are grouped into classes based upon conserved primary and secondary structure and their cognate effector molecule. Although this approach has been very successful in identifying new riboswitch families and defining their distributions, small sequence differences between structurally related RNAs can alter their ligand selectivity and regulatory behavior...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28223907/comparative-bioavailability-and-utilization-of-particular-forms-of-b-12-supplements-with-potential-to-mitigate-b-12-related-genetic-polymorphisms
#16
REVIEW
Cristiana Paul, David M Brady
CONTEXT: Three natural forms of vitamin B12 are commercially available: methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), and hydroxycobalamin (OHCbl), all of which have been shown in clinical studies to improve vitamin B12 status. They are bioidentical to the B12 forms occurring in human physiology and animal foods. In contrast, cyanocobalamin (CNCbl), a synthetic B12 compound used for food fortification and in some supplements, occurs only in trace amounts in human tissues as a result of cyanide intake from smoking or other sources...
February 2017: Integrative Medicine
https://www.readbyqxmd.com/read/28167430/vitamin-b12-in-the-spotlight-again
#17
REVIEW
Jennifer Bridwell-Rabb, Catherine L Drennan
The ability of cobalamin to coordinate different upper axial ligands gives rise to a diversity of reactivity. Traditionally, adenosylcobalamin is associated with radical-based rearrangements, and methylcobalamin with methyl cation transfers. Recently, however, a new role for adenosylcobalamin has been discovered as a light sensor, and a methylcobalamin-dependent enzyme has been identified that is suggested to transfer a methyl anion. Additionally, recent studies have provided a wealth of new information about a third class of cobalamin-dependent enzymes that do not appear to use an upper ligand...
April 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28045498/spectroscopic-studies-of-the-eutt-adenosyltransferase-from-salmonella-enterica-evidence-of-a-tetrahedrally-coordinated-divalent-transition-metal-cofactor-with-cysteine-ligation
#18
Ivan G Pallares, Theodore C Moore, Jorge C Escalante-Semerena, Thomas C Brunold
The EutT enzyme from Salmonella enterica, a member of the family of ATP:cobalt(I) corrinoid adenosyltransferase (ACAT) enzymes, requires a divalent transition metal ion for catalysis, with Fe(II) yielding the highest activity. EutT contains a unique cysteine-rich HX11 CCX2 C(83) motif (where H and the last C occupy the 67th and 83rd positions, respectively, in the amino acid sequence) not found in other ACATs and employs an unprecedented mechanism for the formation of adenosylcobalamin. Recent kinetic and spectroscopic studies of this enzyme revealed that residues in the HX11 CCX2 C(83) motif are required for the tight binding of the divalent metal ion and are critical for the formation of a four-coordinate (4c) cob(II)alamin [Co(II)Cbl] intermediate in the catalytic cycle...
January 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/27858373/vitamin-b12-administration-by-subcutaneous-catheter-device-in-a-cobalamin-a-cbla-patient
#19
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...
2017: 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
#20
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 Salmonella 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...
January 2017: Molecular Microbiology
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