scholarly journals Vitamin B12 Deficiency Induces Imbalance in Melanocytes Homeostasis—A Cellular Basis of Hypocobalaminemia Pigmentary Manifestations

2018 ◽  
Vol 19 (9) ◽  
pp. 2845 ◽  
Author(s):  
Zuzanna Rzepka ◽  
Michalina Respondek ◽  
Jakub Rok ◽  
Artur Beberok ◽  
Keith ó Proinsias ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Scientific Evidence ◽  
Neuropsychiatric Symptoms ◽  
Skin Pigmentation ◽  
Vitamin B12 Deficiency ◽  
Image Cytometry ◽  
B12 Deficiency

Vitamin B12 deficiency causes significant changes in cellular metabolism leading to various clinical symptoms, such as hematological, psychiatric, and neurological disorders. We hypothesize that skin pigmentation disorders may be a diagnostically important manifestation of vitamin B12 deficiency, however the cellular and molecular mechanisms underlying these effects remain unknown. The aim of this study was to examine the effect of vitamin B12 deficiency on melanocytes homeostasis. Hypocobalaminemia in vitro model was developed by treating epidermal melanocytes with synthesized vitamin B12 antagonist—hydroxycobalamin(c-lactam). The cells were examined using immunoenzymatic, spectrophotometric, and fluorimetric assays as well as image cytometry. Significant melanogenesis stimulation—the increase of relative melanin content and tyrosinase activity up to 131% and 135%, respectively—has been indicated. Cobalamin-deficient cells displayed the elevation (by 120%) in reactive oxygen species level. Moreover, the redox status imbalance was stated. The study provided a scientific evidence for melanocytes homeostasis disturbance under hypocobalaminemia, thus indicating a significant element of the hyperpigmentation mechanism due to vitamin B12 deficiency. Furthermore, the implication between pigmentary and hematological and/or neuropsychiatric symptoms in cobalamin-deficient patients may be an important issue.

scholarly journals Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 987-1000 ◽  
Author(s):  
R Carmel ◽  
B Tatsis ◽  
L Baril
Keyword(s):  
Vitamin B12 ◽  
Binding Capacity ◽  
Megaloblastic Anemia ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
High Serum ◽  
The Status ◽  
B12 Deficiency ◽  
Long Acting

A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% of the endogenous vitamin B12 and was not found in his saliva, granulocytes, or urine. This protein was shown to be a complex of TC II and a circulating immunoglobulin (IgGkappa and IgGlambda). Each IgG molecule appeared to bind two TC II molecules. The reacting site did not interfere with the ability of TC II to bind vitamin B12, but did interfere with its ability to transfer the vitamin to cells in vitro. The site was not identical to that reacting with anti-human TC II antibody produced in rabbits. Because of this abnormal complex, 57Co-vitamin B12 injected intravenously was cleared slowly by the patient. However, no metabolic evidence for vitamin B12 deficiency was demonstrable, although the patient initially had megaloblastic anemia apparently due to folate deficiency. The course of the vitamin B12-binding abnormalities was followed over 4 yr and appeared to fluctuate with the status of the patient's illness. The IgG-TC II complex resembled one induced in some patients with pernicious anemia by intensive treatment with long-acting vitamin B12 preparations. The mechanism of induction of the antibody formation in our patient is unknown.

scholarly journals Gel Filtration Studies of Serum B12 Binding: An Abnormal Pattern in Patients with Vitamin B12 Deficiency

Blood ◽  
1969 ◽  
Vol 34 (6) ◽  
pp. 774-781 ◽  
Author(s):  
CHRISTINE LAWRENCE
Keyword(s):  
Molecular Weight ◽  
Vitamin B12 ◽  
Binding Capacity ◽  
Gel Filtration ◽  
Vitamin B12 Deficiency ◽  
Normal Serum ◽  
B12 Deficiency ◽  
Abnormal Pattern ◽  
Normal Controls

Abstract 57CoB12 was added to serum in vitro to study its binding by the three known serum B12-binders in patients with vitamin B12 deficiency and in normal controls. Gel filtration through columns of Sephadex G-200 was used to separate the low (beta) and high (alpha1 and beta) molecular weight B12-binding fractions. Electrophoresis on filter paper was used to separate the alpha1- and beta-globulins. The alpha1-globulin fraction in the serum of B12-deficient patients bound more of the added 57CoB12 than did this fraction in normal serum, presumably because this binder of the serum endogenous vitamin B12 is much less saturated in B12-deficiency. However, the total B12 binding capacity of the alpha1-globulin (for endogenous plus added vitamin B12) was lower in B12-deficient than in normal serum. The low molecular weight beta-binder bound more added 57CoB12 in B12-deficient than in normal serum, whereas the high molecular weight beta binder had a much lower B12-binding capacity in deficient than in normal serum. These abnormalities were independent of the cause of the vitamin B12 deficiency and disappeared after successful treatment with vitamin B12.

scholarly journals Folic acid metabolism in vitamin B12-deficient sheep. Effects of injected methionine on liver constituents associated with folate metabolism

1974 ◽  
Vol 142 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Jeffrey M. Gawthorne ◽  
Richard M. Smith
Keyword(s):  
Vitamin B12 ◽  
Methylenetetrahydrofolate Reductase ◽  
Vitamin B12 Deficiency ◽  
Folate Metabolism ◽  
British Library ◽  
Synthetase Activity ◽  
Intravenous Injections ◽  
B12 Deficiency ◽  
Lending Library

1. A study was made of the effects of injected l-methionine on the activity of several enzymes of folate metabolism, and on the transport of methotrexate in liver preparations from vitamin B12-deficient ewes and their pair-fed controls receiving vitamin B12. 2. The activities of dihydrofolate reductase (EC 1.5.1.3) and 5-methyltetrahydrofolate–homocysteine transmethylase were significantly decreased in the liver of vitamin B12-deficient animals, but were unaffected by l-methionine. 3. The concentration of S-adenosyl-l-methionine in the liver of deficient animals was about one-half of that in normal animals, and was restored to normal by either vitamin B12 or l-methionine. 4. Methylenetetrahydrofolate reductase (EC 1.1.1.68) from sheep liver was inhibited by S-adenosyl-l-methionine in vitro, but not by concentrations of S-adenosyl-l-methionine found in the liver of vitamin B12-deficient animals after injection of physiological amounts of l-methionine. 5. Pteroylpolyglutamate synthetase activity was significantly increased in the liver of vitamin B12-deficient animals, and was decreased by intravenous injections of l-methionine. 6. l-Methionine injections increased the initial rate of uptake of methotrexate in liver slices from deficient animals and acted synergistically with vitamin B12 to increase the quantity taken up in 40min. The failure of folate metabolism in vitamin B12 deficiency can be satisfactorily explained if l-methionine similarly affects the membrane transport of naturally occurring folates. 7. Further details of the results have been deposited as Supplementary Publication SUP 50028 (4 pages) at the British Library (Lending Division), (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1973) 131, 5.

scholarly journals Chronic Atrophic Gastritis Presenting as Hemolytic Anemia due to Severe Vitamin B12 Deficiency

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Amanda M. Woodford ◽  
Rabhea Chaudhry ◽  
Gabriella A. Conte ◽  
Varsha Gupta ◽  
Madhurima Anne
Keyword(s):  
Vitamin B12 ◽  
Atrophic Gastritis ◽  
Hemolytic Anemia ◽  
Neuropsychiatric Symptoms ◽  
Intrinsic Factor ◽  
Vitamin B12 Deficiency ◽  
Disease Process ◽  
Chronic Atrophic Gastritis ◽  
Invasive Treatment ◽  
B12 Deficiency

Vitamin B12 is an essential nutrient which plays an important role in neurological function, hematopoiesis, and DNA synthesis. Low levels usually stem from either poor intake or a malabsorptive process. Presently, the most common cause of vitamin B12 deficiency is food-bound cobalamin malabsorption, which occurs when there is impaired release of vitamin B12 from ingested food due to an outstanding factor preventing the release of the nutrient from its transport protein. Such causes include achlorhydria, gastritis, gastrectomy, or the use of PPIs or antacids. A rarer cause is autoimmune chronic atrophic gastritis, resulting in pernicious anemia. In this disease process, there is destruction of parietal cells and thus a reduction in intrinsic factor, which is essential to the absorption of vitamin B12. Deficiency will result in a variety of abnormalities including but not limited to pancytopenia, paresthesias, and neuropsychiatric symptoms. A rare manifestation of vitamin B12 deficiency is hemolytic anemia, which occurs due to intramedullary and extramedullary dysfunction. This case describes a 46-year-old male with no past medical history who presented with chest pain, fatigue, and progressive weakness, found to have hemolytic anemia, ultimately attributed to vitamin B12 deficiency. Antiparietal cell antibodies and intrinsic factor antibodies (IFA) were both negative. Still, the patient underwent an endoscopy with biopsies of the stomach; pathology was consistent with chronic metaplastic atrophic gastritis. The patient improved with intramuscular vitamin B12 supplementation. This case highlights both a rare cause and presentation of vitamin B12 deficiency. Patients with autoimmune chronic atrophic gastritis should have antiparietal cell or intrinsic factor antibodies. Still, seronegative patients have been reported, like this patient. Additionally, hemolytic anemia secondary to vitamin B12 deficiency is uncommon. The presentation will usually mirror that of a thrombotic microangiopathy (TMA), including hemolytic anemia with schistocytes on peripheral blood smear and thrombocytopenia, as it did in this patient. This clinical entity is described as pseudothrombotic microangiopathy and is crucial to identify in order to prevent the initiation of invasive treatment strategies such as plasmapheresis.

scholarly journals Reduced Methionine Synthase (Mtr) Expression, a Model of Vitamin B12 Deficiency, Leads to Uracil Accumulation in Mitochondrial and Nuclear DNA

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1314-1314
Author(s):  
Katarina Heyden ◽  
Yuwen Xiu ◽  
Martha Field
Keyword(s):  
Vitamin B12 ◽  
Nuclear Dna ◽  
Functional Model ◽  
Vitamin B12 Deficiency ◽  
Water Soluble ◽  
Methionine Synthase ◽  
Nucleotide Synthesis ◽  
Carbon Transfer ◽  
B12 Deficiency

Abstract Objectives Integrity of both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) is affected by nutritional and environmental factors. Folate and B12 are water-soluble B-vitamins that act as cofactors in folate-mediated one-carbon metabolism (FOCM), a series of one-carbon transfer reactions that support several essential cell processes including nucleotide biosynthesis. Impairments in FOCM, such as folate or vitamin B12 deficiency, can disturb thymidylate (dTMP, the “T” base in DNA) synthesis and lead to uracil misincorporation to DNA. Both folate and B12 deficiency as well as genetic polymorphisms affecting FOCM function are associated with increased uracil accumulation and DNA damage in nDNA. However, dTMP synthesis occurs in multiple cellular compartments (cytosol, nucleus, and mitochondria), and it is not well defined how FOCM impairments affects mtDNA integrity and nucleotide pool balance between compartments. Methods Currently, we are using in vivo and in vitro experiments to assess nucleotide synthesis and uracil accumulation in a functional model of vitamin B-12 deficiency with decreased expression of methionine synthase (Mtr), one of two B12-requiring enzymes. Tissues from Mtr+/+,+/− mice and Mtr+/+,+/-  mouse-derived cells were exposed to either folate-replete or folate-deplete conditions to explore the combined effects of folate and B12 deficiency on nucleotide synthesis capacity and integrity of both nDNA and mtDNA. Results We have developed and validated a novel real-time PCR-based assay to quantify uracil misincorporation into mtDNA. In mouse liver, we observed a significant increase of uracil in mtDNA with decreased Mtr expression as well as an interaction between Mtr genotype and folate status. Mouse embryonic fibroblasts (MEFs) demonstrated perturbed dTMP synthesis and increased uracil accumulation in nDNA with decreased Mtr expression. Conclusions These data suggest that functional B12 deficiency, as modeled by decreased Mtr expression, disrupts nucleotide synthesis in more than one cellular compartment and increases uracil accumulation not only in nDNA, but also in mtDNA. Reduced Mtr expression may cause a redistribution of folates in the cytoplasm which impacts mitochondrial folate levels, and subsequently mitochondrial dTMP synthesis. Funding Sources N/A.

scholarly journals Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 987-1000 ◽  
Author(s):  
R Carmel ◽  
B Tatsis ◽  
L Baril
Keyword(s):  
Vitamin B12 ◽  
Binding Capacity ◽  
Megaloblastic Anemia ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
High Serum ◽  
The Status ◽  
B12 Deficiency ◽  
Long Acting

Abstract A patient with recurrent pulmonary abscess, weight loss, and alcoholism was found to have extremely high serum vitamin B12 and unsaturated vitamin B12-binding capacity (UBBC) levels. While transcobalamin (TC) II was also increased, most of his UBBC was due to an abnormal binding protein which carried greater than 80% of the endogenous vitamin B12 and was not found in his saliva, granulocytes, or urine. This protein was shown to be a complex of TC II and a circulating immunoglobulin (IgGkappa and IgGlambda). Each IgG molecule appeared to bind two TC II molecules. The reacting site did not interfere with the ability of TC II to bind vitamin B12, but did interfere with its ability to transfer the vitamin to cells in vitro. The site was not identical to that reacting with anti-human TC II antibody produced in rabbits. Because of this abnormal complex, 57Co-vitamin B12 injected intravenously was cleared slowly by the patient. However, no metabolic evidence for vitamin B12 deficiency was demonstrable, although the patient initially had megaloblastic anemia apparently due to folate deficiency. The course of the vitamin B12-binding abnormalities was followed over 4 yr and appeared to fluctuate with the status of the patient's illness. The IgG-TC II complex resembled one induced in some patients with pernicious anemia by intensive treatment with long-acting vitamin B12 preparations. The mechanism of induction of the antibody formation in our patient is unknown.

scholarly journals Clinical and Brain Imaging Findings in a Child with Vitamin B12 Deficiency

2021 ◽  
Vol 13 (4) ◽  
pp. 583-588
Author(s):  
Paola Feraco ◽  
Francesca Incandela ◽  
Roberto Franceschi ◽  
Cesare Gagliardo ◽  
Maria Bellizzi
Keyword(s):  
Vitamin B12 ◽  
Brain Atrophy ◽  
Clinical Symptoms ◽  
Vitamin B12 Deficiency ◽  
Brain Magnetic Resonance Imaging ◽  
Failure To Thrive ◽  
Neurological Symptoms ◽  
Vegan Diet ◽  
Mri Findings ◽  
B12 Deficiency

Vitamin B12 (Vit-B12) deficiency is a rare and treatable cause of failure to thrive and delayed development in infants who are exclusively breastfed. Apart from genetic causes, it can be related to a malabsorption syndrome or when the mother follows a strict vegetarian or vegan diet, causing a low hepatic storage of Vit-B12 in the infant at birth. As the neurological symptoms are nonspecific, a brain magnetic resonance imaging (MRI) exam is usually performed to rule out primary causes of neurodevelopmental delay. Findings related to brain atrophy are usually observed. A favorable response is achieved with Vit-B12 therapy, and neurological symptoms dramatically improve within a few days after the treatment. We present the case of an infant with severe Vit-B12 deficiency, exclusively breastfed by his young vegan mother, and whose clinical symptoms together with MRI findings improved after treatment. Brain atrophy recovery after Vit-B12 therapy has been seldom documented.

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