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Hathairat Sawaengsri, Peter R Bergethon, Wei Qiao Qiu, Tammy M Scott, Paul F Jacques, Jacob Selhub, Ligi Paul
BACKGROUND: The 776C→G polymorphism of the vitamin B-12 transport protein transcobalamin gene (TCN2) (rs1801198; Pro259Arg) is associated with a lower holotranscobalamin concentration in plasma. This effect may reduce the availability of vitamin B-12 to tissues even when vitamin B-12 intake is adequate. Clinical outcomes associated with vitamin B-12 insufficiency could potentially be worsened by high folate intake. OBJECTIVE: We determined the association of the TCN2 776C→G polymorphism and folate intake with peripheral neuropathy in elders with normal plasma concentrations of vitamin B-12...
October 12, 2016: American Journal of Clinical Nutrition
Omar Abuyaman, Niels Torring, Rima Obeid, Ebba Nexo
BACKGROUND: Human placenta expresses CD320, a receptor that ensures the uptake of holo-transcobalamin (holoTC). Soluble CD320 (sCD320) is present in the circulation and its concentration increases during pregnancy. AIMS: To investigate a possible association of sCD320, holoTC and total transcobalamin (TC) with the risk of subsequent preeclampsia using serum samples from asymptomatic first trimester pregnant women. Moreover, we aimed to establish reference intervals of the aforementioned biomarkers for first trimester pregnant women who remained healthy throughout pregnancy...
October 4, 2016: Scandinavian Journal of Clinical and Laboratory Investigation
Alexander J Layden, Kimberly O O'Brien, Eva K Pressman, Elizabeth M Cooper, Tera R Kent, Julia L Finkelstein
BACKGROUND: Transcobalamin is a key placental protein involved in transport of vitamin B12 to the fetus. However, few data currently exist on the ability of the placenta to modify vitamin B12 transporter expression, particularly in high-risk populations such as pregnant adolescents. OBJECTIVE: This study was conducted to determine the impact of maternal and neonatal serum vitamin B12 concentrations on placental transcobalamin (TC) expression in a cohort of healthy pregnant adolescents in the United States...
September 2016: Placenta
S Z Zheng, X P Xia, H Wu, X X Shao, X Q Lin, X L Wu, L J Jiang, R Ding, Y Jiang
OBJECTIVE: To investigate the association of Crohn's disease (CD) with transcobalamin Ⅱ (TCN2) gene polymorphisms and serum homocysteine (Hcy), folate, and vitamin B12 levels in Chinese patients. METHODS: In a total of 307 CD patients (CD group) and 574 healthy controls (control group) of Han ethnicity selected at 4 hospitals in Wenzhou between January 2007 and August 2015, TCN2 gene polymorphisms (rs1801198, C/G; rs9606756, A/G) in peripheral blood were determined using improved multiple ligase detection reaction (iMLDR)...
August 9, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Luciana Hannibal, Vegard Lysne, Anne-Lise Bjørke-Monsen, Sidney Behringer, Sarah C Grünert, Ute Spiekerkoetter, Donald W Jacobsen, Henk J Blom
Vitamin B12 (cobalamin, Cbl, B12) is an indispensable water-soluble micronutrient that serves as a coenzyme for cytosolic methionine synthase (MS) and mitochondrial methylmalonyl-CoA mutase (MCM). Deficiency of Cbl, whether nutritional or due to inborn errors of Cbl metabolism, inactivate MS and MCM leading to the accumulation of homocysteine (Hcy) and methylmalonic acid (MMA), respectively. In conjunction with total B12 and its bioactive protein-bound form, holo-transcobalamin (holo-TC), Hcy, and MMA are the preferred serum biomarkers utilized to determine B12 status...
2016: Frontiers in Molecular Biosciences
Amer Alam, Jae-Sung Woo, Jennifer Schmitz, Bernadette Prinz, Katharina Root, Fan Chen, Joël S Bloch, Renato Zenobi, Kaspar P Locher
Cellular uptake of vitamin B12 (cobalamin) requires capture of transcobalamin (TC) from the plasma by CD320, a ubiquitous cell surface receptor of the LDLR family. Here we present the crystal structure of human holo-TC in complex with the extracellular domain of CD320, visualizing the structural basis of the TC-CD320 interaction. The observed interaction chemistry can rationalize the high affinity of CD320 for TC and lack of haptocorrin binding. The in vitro affinity and complex stability of TC-CD320 were quantitated using a solid-phase binding assay and thermostability analysis...
2016: Nature Communications
Paul Henry Golding
The concentration of total vitamin B12 in serum is not a sufficiently sensitive or specific indicator for the reliable diagnosis of vitamin B12 deficiency. Victor Herbert proposed a model for the staged development of vitamin B12 deficiency, in which holotranscobalamin (HoloTC) is the first indicator of deficiency. Based on this model, a commercial immunoassay has been controversially promoted as a replacement for the total vitamin B12 test. HoloTC is cobalamin (vitamin B12) attached to the transport protein transcobalamin, in the serum, for delivery to cells for metabolism...
2016: SpringerPlus
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
Osama Y Al-Dirbashi, Nathan McIntosh, Pranesh Chakraborty
BACKGROUND: Newborn screening for propionic acidemia and methylmalonic acidurias using the marker propionylcarnitine (C3) is neither sensitive nor specific. Using C3 to acetylcarnitine (C3/C2) ratio, together with conservative C3 cut-offs, can improve screening sensitivity, but the false positive rate remains high. Incorporating the marker 2-methylcitric acid has been suggested, to improve the positive predictive value for these disorders without compromising the sensitivity. METHODS: Between July 2011 and December 2012 at the Newborn Screening Ontario laboratory, all neonatal dried blood spot samples that were reported as screen positive for propionic acidemia or methylmalonic acidurias based on elevated C3 and C3/C2 ratio were analyzed for 2-methylcitric acid, using liquid chromatography tandem mass spectrometry...
May 22, 2016: Journal of Medical Screening
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
Peter Keller, Janine Rufener, Christof Schild, Sergey N Fedosov, Peter H Nissen, Ebba Nexo
BACKGROUND: Measurement of holotranscobalamin (holoTC) is increasingly used as a screening test for cobalamin (Cbl) deficiency. A level well below the reference interval strongly supports a deficient state. We examined a 21-year-old woman diagnosed as Cbl deficient because of an extremely low holoTC level as measured by the Abbott Architect Assay. METHODS: The patient was evaluated for Cbl deficiency employing an in-house holoTC method as well as other routine markers of Cbl status...
May 6, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Trayambak Basak, Gaurav Garg, Nitin Bhardwaj, Vinay Singh Tanwar, Sandeep Seth, Ganesan Karthikeyan, Shantanu Sengupta
Coronary artery disease (CAD) has been increasing alarmingly in India. We had earlier shown that vitamin B12 deficiency is associated with CAD in Indian population. However, only about a quarter of the total vitamin B12 is internalised in the cells by the proteins transcobalamin II. Vitamin B12-bound transcobalamin II (holotranscobalamin, holoTC) is thus referred to as biologically active B12. In this study, we ascertained the levels of holoTC in 501 CAD cases and 1253 healthy controls and for the first time show that holoTC levels are significantly lower (p = 2...
July 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Agata Sobczyńska-Malefora, Faith Pangilinan, Gordon T Plant, Aneliya Velkova, Dominic J Harrington, Anne M Molloy, Lawrence C Brody
BACKGROUND: The clinical use of holotranscobalamin (holoTC) testing to evaluate vitamin B12 status has increased in recent years. We present two patients (African Caribbean and Indian heritage), in which the holoTC assay indicated severe B12 deficiency (< 5 pmol/L). Additional clinical tests revealed that these patients had normal levels of total vitamin B12 in blood and unremarkable levels of two other markers of vitamin B12 status, homocysteine and methylmalonic acid. We hypothesized that these patients carry a variant in the transcobalamin gene (TCN2) that influences the most widely commercially available holoTC test - Active-B12 (Axis-Shield Diagnostics Ltd)...
May 2016: European Journal of Clinical Investigation
L S Kornerup, C B Juul, S N Fedosov, C W Heegaard, E Greibe, E Nexo
INTRODUCTION: Cobalamin/Vitamin B12 (Cbl) is an essential vitamin, supplied mainly as hydroxocobalamin (OHCbl) by animal products, including cows' milk. Cyanocobalamin (CNCbl) is the usual form in vitamin pills. The aim was to explore absorption and tissue accumulation of two Cbl forms, administered alone or bound to milk protein. MATERIALS AND METHODS: We synthesized labeled OH[(57)Co]Cbl from commercially available CN[(57)Co]Cbl. Recombinant bovine transcobalamin (rbTC) was produced in yeast and skimmed milk obtained off the shelf...
July 2016: Biochimie
David H Alpers
The systems involving folate and cobalamin have several features in common: 1) their dietary forms require luminal digestion for absorption; 2) intestinal bacteria in the upper intestine synthesize and utilize both vitamins, creating possible competition for the nutrients; 3) there is one major intestinal brush border protein essential for absorption; 4) both are subject to extensive entero-hepatic circulation. Finally, human mutations have confirmed the role of specific transporters and receptors in these processes...
July 2016: Biochimie
Omar Abuyaman, Ebba Nexo
BACKGROUND: Cellular uptake of vitamin B12 (B12) demands binding of the vitamin to transcobalamin (TC) and recognition of TC-B12 (holoTC) by the receptor CD320. Recently, we identified a soluble form of CD320 (sCD320) in human plasma. Here we present data on the occurrence of this soluble receptor in cerebrospinal fluid (CSF) and show its correlations to dementia-related biomarkers tau proteins and amyloid-beta. METHODS: We collected 223 cerebrospinal fluid samples and corresponding plasma samples (n = 46)...
October 2015: Scandinavian Journal of Clinical and Laboratory Investigation
Paul A Dutchak, Sunil Laxman, Sandi Jo Estill, Chensu Wang, Yun Wang, Yiguang Wang, Gamze B Bulut, Jinming Gao, Lily J Huang, Benjamin P Tu
Nitrogen permease regulator-like 2 (NPRL2) is a component of a conserved complex that inhibits mTORC1 (mammalian Target Of Rapamycin Complex 1) in response to amino acid insufficiency. Here, we show that NPRL2 is required for mouse viability and that its absence significantly compromises fetal liver hematopoiesis in developing embryos. Moreover, NPRL2 KO embryos have significantly reduced methionine levels and exhibit phenotypes reminiscent of cobalamin (vitamin B12) deficiency. Consistent with this idea, NPRL2 KO liver and mouse embryonic fibroblasts (MEFs) show defective processing of the cobalamin-transport protein transcobalamin 2, along with impaired lysosomal acidification and lysosomal gene expression...
July 21, 2015: Cell Reports
Ting-Yuan David Cheng, Karen W Makar, Marian L Neuhouser, Joshua W Miller, Xiaoling Song, Elissa C Brown, Shirley A A Beresford, Yingye Zheng, Elizabeth M Poole, Rachel L Galbraith, David J Duggan, Nina Habermann, Lynn B Bailey, David R Maneval, Marie A Caudill, Adetunji T Toriola, Ralph Green, Cornelia M Ulrich
BACKGROUND: Investigations of folate-mediated one-carbon metabolism (FOCM) genes and gene-nutrient interactions with respect to colorectal cancer (CRC) risk are limited to candidate polymorphisms and dietary folate. This study comprehensively investigated associations between genetic variants in FOCM and CRC risk and whether the FOCM nutrient status modified these associations. METHODS: Two hundred eighty-eight candidate and tagging single-nucleotide polymorphisms (SNPs) in 30 FOCM genes were genotyped for 821 incident CRC case-control matched pairs in the Women's Health Initiative Observational Study cohort...
October 15, 2015: Cancer
Stephen D Merrigan, William E Owen, Joely A Straseski
BACKGROUND: Vitamin B12 (cobalamin) is a necessary cofactor in methionine and succinyl-CoA metabolism. Studies estimate the deficiency prevalence as high as 30% in the elderly population. Ten to thirty percent of circulating cobalamin is bound to transcobalamin (holotranscobalamin, holoTC) which can readily enter cells and is therefore considered the bioactive form. The objective of our study was to evaluate the analytical performance of a high-throughput, automated holoTC assay (ARCHITECT i2000(SR) Active-B12 (Holotranscobalamin)) and compare it to other available methods...
2015: Clinical Laboratory
Sandip Bartakke, Avinash Saindane, Vardhaman Udgirkar, S Shrividya, Gandham SriLakshmi Bhavani, Katta M Girisha
No abstract text is available yet for this article.
November 2015: Indian Journal of Pediatrics
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