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https://www.readbyqxmd.com/read/29132166/congenital-transcobalamin-ii-deficiency-a-rare-entity-with-a-broad-differential
#1
Mwe Mwe Chao, Sabine Illsinger, Ayami Yoshimi, Anibh Martin Das, Christian Peter Kratz
No abstract text is available yet for this article.
November 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/29104950/-89-zr-cobalamin-pet-tracer-synthesis-cellular-uptake-and-use-for-tumor-imaging
#2
Akhila N W Kuda-Wedagedara, Jayme L Workinger, Ebba Nexo, Robert P Doyle, Nerissa Viola-Villegas
Vitamin B12, or cobalamin (Cbl), is an essential nutrient. Acquisition, transport, and cellular internalization of Cbl are dependent on specific binding proteins and associated receptors. The circulating transport protein transcobalamin (TC) promotes cellular uptake via binding to specific receptors such as CD320, a receptor upregulated in several cancer cell lines. In this study, we report the successful synthesis of (89)Zirconium-labeled Cbl that was derivatized with desferrioxamine ((89)Zr-Cbl). We document the purity of the tracer and its binding to TC compared with that of unmodified cyano-Cbl (CN-Cbl)...
October 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/29040465/the-fut2-secretor-variant-p-trp154ter-influences-serum-vitamin-b12-concentration-via-holo-haptocorrin-but-not-holo-transcobalamin-and-is-associated-with-haptocorrin-glycosylation
#3
Aneliya Velkova, Jennifer E L Diaz, Faith Pangilinan, Anne M Molloy, James L Mills, Barry Shane, Erica Sanchez, Conal Cunningham, Helen McNulty, Cheryl D Cropp, Joan E Bailey-Wilson, Alexander F Wilson, Lawrence C Brody
Vitamin B12 deficiency is common in older individuals. Circulating vitamin B12 concentration can be used to diagnose deficiency but this test has substantial false positive and false negative rates. We conducted genome-wide association studies (GWAS) in which we resolved total serum vitamin B12 into the fractions bound to transcobalamin and haptocorrin: two carrier proteins with very different biological properties. We replicated reported associations between total circulating vitamin B12 concentrations and a common null variant in FUT2...
October 12, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28981944/-association-of-transcobalamine-ii-gene-polymorphisms-and-serum-homocysteine-vitamin-b12-and-folate-levels-with-ulcerative-colitis-among-chinese-patients
#4
Shuzi Zheng, Hao Wu, Fangpeng Ye, Xuanping Xia, Shenglong Xia, Xiuqing Lin, Xiaoli Wu, Lijia Jiang, Ran Ding, Yi Jiang
OBJECTIVE: To assess the association of transcobalamine II (TCN2) gene polymorphisms and serum levels of homocysteine (Hcy), vitamin B12 and folate with ulcerative colitis (UC) among Chinese patients. METHODS: For 397 UC patients and 574 controls, two single nucleotide polymorphisms of the TCN2 gene (rs1801198, rs9606756) were tested with an improved multiple ligase detection reaction method. Serum Hcy, vitamin B12 and folate were measured with an enzymatic cycling assay and an chemiluminescence immunoassay, respectively...
October 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28975627/meat-consumption-during-pregnancy-and-substance-misuse-among-adolescent-offspring-stratification-of-tcn2-genetic-variants
#5
Joseph R Hibbeln, John Paul SanGiovanni, Jean Golding, Pauline M Emmett, Kate Northstone, John M Davis, Marc Schuckit, Jon Heron
BACKGROUND: Reducing meat consumption is often advised; however, inadvertent nutritional deficiencies during pregnancy may result in residual neurodevelopmental harms to offspring. This study assessed possible effects of maternal diets in pregnancy on adverse substance use among adolescent offspring. METHODS: Pregnant women and their 13-year-old offspring taking part in a prospective birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC), provided Food Frequency Questionnaire data from which dietary patterns were derived using principal components analysis...
November 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28910388/structure-of-the-human-transcobalamin-beta-domain-in-four-distinct-states
#6
Joël S Bloch, Markus Ruetz, Bernhard Kräutler, Kaspar P Locher
Vitamin B12 (cyanocobalamin, CNCbl) is an essential cofactor-precursor for two biochemical reactions in humans. When ingested, cobalamins (Cbl) are transported via a multistep transport system into the bloodstream, where the soluble protein transcobalamin (TC) binds Cbl and the complex is taken up into the cells via receptor mediated endocytosis. Crystal structures of TC in complex with CNCbl have been solved previously. However, the initial steps of holo-TC assembly have remained elusive. Here, we present four crystal structures of the beta domain of human TC (TC-beta) in different substrate-bound states...
2017: PloS One
https://www.readbyqxmd.com/read/28903415/a-missense-mutation-in-tcn2-is-associated-with-decreased-risk-for-congenital-heart-defects-and-may-increase-cellular-uptake-of-vitamin-b12-via-megalin
#7
Peiqiang Li, Lijuan Huang, Yufang Zheng, Xuedong Pan, Rui Peng, Yueming Jiang, Richard H Finnell, Haijie Li, Bin Qiao, Hong-Yan Wang
Deregulation of folate and vitamin B12 (VB12) metabolism contributes to the risk of congenital heart defects (CHDs). Transcobalamin (TCN2) is essential for transporting VB12 from blood to cells as TCN2-bound VB12 (holo-TC) is the only form for somatic cellular uptake. In this study, we performed an association study between common polymorphisms in 46 one carbon metabolism genes and CHD in 412 CHDs and 213 controls. Only two significant association signals in coding regions were identified: FTCD c.1470C>T & TCN2 c...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881087/organometallic-dna-b12-conjugates-as-potential-oligonucleotide-vectors-synthesis-and-structural-and-binding-studies-with-human-cobalamin-transport-proteins
#8
Elena Mutti, Miriam Hunger, Sergey Fedosov, Ebba Nexo, Bernhard Kräutler
The synthesis and structural characterization of Co-(dN)25 -Cbl (Cbl: cobalamin; dN: deoxynucleotide) and Co-(dN)39 -Cbl, which are organometallic DNA-B12 conjugates with single DNA strands consisting of 25 and 39 deoxynucleotides, respectively, and binding studies of these two DNA-Cbl conjugates to three homologous human Cbl transporting proteins, transcobalamin (TC), intrinsic factor (IF), and haptocorrin (HC), are reported. This investigation tests the suitability of such DNA-Cbls for the task of eventual in vivo oligonucleotide delivery...
September 7, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28814397/association-of-tcn2-rs1801198-c-776g-c-polymorphism-with-markers-of-one-carbon-metabolism-and-related-diseases-a-systematic-review-and-meta-analysis-of-genetic-association-studies
#9
REVIEW
Abderrahim Oussalah, Julien Levy, Pierre Filhine-Trésarrieu, Fares Namour, Jean-Louis Guéant
Background: Vitamin B-12 (cobalamin) deficiency may produce severe neurologic and hematologic manifestations. Approximately 20-25% of circulating cobalamin binds to transcobalamin 2 (TCN2), which is referred to as active vitamin B-12. The G allele of the TCN2 c.776G>C (rs1801198) polymorphism has been associated with a lower plasma concentration of holotranscobalamin. However, genotype association studies on rs1801198 have led to conflicting results regarding its influence on one-carbon metabolism (OCM) markers or its association with pathologic conditions...
October 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28746916/a-missense-mutation-in-tcn2-is-associated-with-decreased-risk-for-congenital-heart-defects-and-may-increase-cellular-uptake-of-vitamin-b12-via-megalin
#10
Peiqiang Li, Lijuan Huang, Yufang Zheng, Xuedong Pan, Rui Peng, Yueming Jiang, Richard H Finnell, Haijie Li, Bin Qiao, Hong-Yan Wang
Deregulation of folate and vitamin B12 (VB12) metabolism contributes to the risk of congenital heart defects (CHDs). Transcobalamin (TCN2) is essential for transporting VB12 from blood to cells as TCN2-bound VB12 (holo-TC) is the only form for somatic cellular uptake. In this study, we performed an association study between common polymorphisms in 46 one carbon metabolism genes and CHD in 412 CHDs and 213 controls. Only two significant association signals in coding regions were identified: FTCD c.1470C>T & TCN2 c...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28660890/vitamin-b12-deficiency
#11
REVIEW
Ralph Green, Lindsay H Allen, Anne-Lise Bjørke-Monsen, Alex Brito, Jean-Louis Guéant, Joshua W Miller, Anne M Molloy, Ebba Nexo, Sally Stabler, Ban-Hock Toh, Per Magne Ueland, Chittaranjan Yajnik
Vitamin B12 (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals...
June 29, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28638446/overexpression-of-transcobalamin-1-is-an-independent-negative-prognosticator-in-rectal-cancers-receiving-concurrent-chemoradiotherapy
#12
Yi-Ying Lee, Yu-Ching Wei, Yu-Feng Tian, Ding-Ping Sun, Ming-Jen Sheu, Ching-Chieh Yang, Li-Ching Lin, Chen-Yi Lin, Chung-Hsi Hsing, Wan-Shan Li, Chien-Feng Li, Pei-Ling Hsieh, Ching-Yih Lin
Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28545069/behavioral-alterations-are-associated-with-vitamin-b12-deficiency-in-the-transcobalamin-receptor-cd320-ko-mouse
#13
Kaveri Arora, Jeffrey M Sequeira, Alejandro I Hernández, Juan M Alarcon, Edward V Quadros
Vitamin B12 (cobalamin) deficiency is prevalent worldwide and causes megaloblastic anemia and neurologic deficits. While the anemia can be treated, the neurologic deficits can become refractive to treatment as the disease progresses. Therefore, timely intervention is critical for a favorable outcome. Moreover, the metabolic basis for the neuro-pathologic changes and the role of cobalamin deficiency in the pathology still remains unexplained. Using a transcobalamin receptor / CD320 knockout mouse that lacks the receptor for cellular uptake of transcobalamin bound cobalamin, we aimed to determine whether cobalamin deficiency in the central nervous system produced functional neurologic deficits in the mouse that would parallel those observed in humans...
2017: PloS One
https://www.readbyqxmd.com/read/28538514/long-term-outcome-of-4-patients-with-transcobalamin-deficiency-caused-by-2-novel-tcn2-mutations
#14
Marwan Nashabat, Gustavo Maegawa, Peter H Nissen, Ebba Nexo, Hussain Al-Shamrani, Mohammed Al-Owain, Majid Alfadhel
Cobalamin (vitamin B12 [Cbl]) is an essential cofactor for many biochemical pathways. Transcobalamin (TC) is required to internalize Cbl into the cells through membrane receptor-mediated endocytosis. Cbl is then processed in the cytoplasm and mitochondria by complementation factors leading to its active metabolites; methylcobalamin and 5-deoxyadenosyl-cobalamin. Deficiency of TC results in an elevation in methylmalonic acid and homocysteine. Patients usually present with macrocytic anemia, pancytopenia, failure to thrive, gastrointestinal symptoms, and neurological dysfunction...
November 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28526947/association-of-ulcerative-colitis-with-transcobalamin-ii-gene-polymorphisms-and-serum-homocysteine-vitamin-b12-and-folate-levels-in-chinese-patients
#15
Shuzi Zheng, Wei Yang, Chaoqun Wu, Liang Sun, Daopo Lin, Xiuqing Lin, Lijia Jiang, Ran Ding, Yi Jiang
It has been reported that abnormal elevation of homocysteine is quite prevalent in ulcerative colitis (UC) patients. We attempted to explore the relationship of UC with transcobalamin II (TCN2) gene polymorphisms and serum homocysteine, vitamin B12, and folate levels in Chinese patients. TCN2 (rs1801198, rs9606756) genotypes were detected by the improved multiple ligase detection reaction (iMLDR) technique in 527 UC patients and 574 controls. Moreover, 128 UC patients and 138 controls were randomly selected for the measurement of homocysteine, vitamin B12, and folate levels by enzymatic cycling assay or chemiluminescence immunoassay...
July 2017: Immunogenetics
https://www.readbyqxmd.com/read/28522466/trilineage-dyspoiesis-caused-by-transcobalamin-ii-deficiency
#16
Weijie Li, Derrick Goubeaux
No abstract text is available yet for this article.
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28486088/the-soluble-transcobalamin-receptor-scd320-in-relation-to-alzheimer-s-disease-and-cognitive-scores
#17
Omar Abuyaman, Marc Combrinck, A David Smith, Ebba Nexo
The soluble transcobalamin receptor (sCD320) is present in cerebrospinal fluid and correlates with the dementia-related biomarkers phospho-tau and total-tau. Here we present data on the relation of sCD320 to Alzheimer's disease and scores of cognitive tests. Lumbar cerebrospinal fluid samples from 42 pathologically-confirmed cases of Alzheimer's disease and 25 non-demented controls were analyzed for sCD320 employing an in-house ELISA. The participants' cognitive functions were tested using the Cambridge Cognition Examination (CAMCOG) and the Mini-Mental State Examination (MMSE)...
May 9, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28472811/an-analysis-of-transcobalamin-ii-gene-polymorphisms-and-serum-levels-of-homocysteine-folate-and-vitamin-b12-in-chinese-patients-with-crohn-s-disease
#18
Shuzi Zheng, Chaoqun Wu, Wei Yang, Xuanping Xia, Xiuqing Lin, Lijia Jiang, Ran Ding, Yi Jiang
OBJECTIVES: The study aimed to investigate the association of Crohn's disease (CD) with transcobalamin II (TCN2) polymorphisms and serum homocysteine, folate, and vitamin B12 levels. METHODS: TCN2 (rs1801198, rs9606756) were genotyped by iMLDR in 389 CD patients and 746 controls. Furthermore, 102 CD patients and 153 controls were randomly selected for examination of serum homocysteine, folate, and vitamin B12 levels by enzymatic cycling assay and chemiluminescence immunoassay, respectively...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28351841/maternofetal-transport-of-vitamin-b12-role-of-tcblr-cd320-and-megalin
#19
Kaveri Arora, Jeffrey M Sequeira, Edward V Quadros
Vitamin B12 deficiency causes megaloblastic anemia and neurologic disorder in humans. Gene defects of transcobalamin (TC) and the transcobalamin receptor (TCblR), needed for cellular uptake of the TC-bound B12, do not confer embryonic lethality. TC deficiency can produce the hematologic and neurologic complications after birth, whereas TCblR/CD320 gene defects appear to produce mild metabolic changes. Alternate maternofetal transport mechanisms appear to provide adequate B12 to the fetus. To understand this mechanism, we evaluated the role of TC, TCblR/CD320, and megalin in maternofetal transport of B12 in a TCblR/CD320-knockout (KO) mouse...
July 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28321545/tissue-distribution-of-oral-vitamin-b12-is-influenced-by-b12-status-and-b12-form-an-experimental-study-in-rats
#20
Linda S Kornerup, Sergey N Fedosov, Christian B Juul, Eva Greibe, Christian W Heegaard, Ebba Nexo
PURPOSE: Hydroxocobalamin (HOCbl) is the dominating Cbl form in food, whereas cyanocobalamin (CNCbl) is common in vitamin pills and oral supplements. This study compares single-dose absorption and distribution of oral HO[(57)Co]Cbl and CN[(57)Co]Cbl in Cbl-deficient and normal rats. METHODS: Male Wistar rats (7 weeks) were fed a 14-day diet with (n = 15) or without (n = 15) Cbl. We compared the uptakes of HO[(57)Co]Cbl (free or bound to bovine transcobalamin) and free CN[(57)Co]Cbl administered by gastric gavage (n = 5 in each diet group)...
March 20, 2017: European Journal of Nutrition
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