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 Perspective: Practical Approach to Preventing Subclinical B12 Deficiency in Elderly Population

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1913
Author(s):  
Alessandra Vincenti ◽  
Laura Bertuzzo ◽  
Antonio Limitone ◽  
Giuseppe D’Antona ◽  
Hellas Cena
Keyword(s):  
Vitamin B12 ◽  
Elderly Population ◽  
Vitamin B12 Deficiency ◽  
Water Soluble ◽  
Health Issues ◽  
Animal Products ◽  
Water Soluble Vitamin ◽  
Age Dependent ◽  
B12 Deficiency ◽  
Inadequate Dietary Intake

Vitamin B12 (also known as cobalamin) is an essential water-soluble vitamin that plays a pivotal role for several physiologic functions during one’s lifespan. Only certain microorganisms are able to synthetize B12, thus humans obtain cobalamin exclusively from their diet, specifically from animal-derived foods. Specific sub-group populations are at risk of vitamin B12 subclinical deficiency due to different factors including poor intake of animal source foods and age-dependent decrease in the capacity of intestinal B12 uptake. Consumption of animal products produces some negative health issues and negatively impacts sustainability while a plant-based diet increases the risk of B12 deficiency. Taking a cue from the aforementioned considerations, this narrative review aims to summarize facts about B12 deficiency and the burden of inadequate dietary intake in elderly population, as well as to discuss sustainable approaches to vitamin B12 deficiency in aging population.

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 Vitamin B12 deficiency: metabolic effects, clinical evaluation, and treatment

2019 ◽  
Vol 59 (2) ◽  
pp. 40 ◽  
Author(s):  
Synara Cavalcante Lopes ◽  
Daniel Duarte Gadelha ◽  
Manuela Dias de Carvalho ◽  
Virgínia Oliveira Fernandes ◽  
Renan Magalhães Montenegro Junior
Keyword(s):  
Insulin Resistance ◽  
Vitamin B12 ◽  
Neurological Disorders ◽  
Vitamin B12 Deficiency ◽  
The Body ◽  
Water Soluble ◽  
Metabolic Effects ◽  
Pharmacological Treatments ◽  
B12 Deficiency ◽  
Composition Changes

Vitamin B12 is a water-soluble essential micronutrient, required by all the body cells. Its deficiency has been implicated not only in hematological and neurological disorders, but also in many metabolic processes, such as insulin resistance and body composition changes, which have aroused particular interest in recent years. This study reviews the physiology of vitamin B12 from its digestion and absorption to its distribution in tissues, metabolic effects and controversies regarding the diagnosis of deficiency, and to dietary and pharmacological treatments.

scholarly journals Biochemical Impedance on Intracellular Functions of Vitamin B12 in Chronic Toxigenic Mold Exposures

2007 ◽  
Vol 7 ◽  
pp. 1649-1657 ◽  
Author(s):  
Ebere C. Anyanwu ◽  
Ijeoma Kanu
Keyword(s):  
Vitamin B12 ◽  
Neurological Disorders ◽  
Vitamin B12 Deficiency ◽  
Methionine Synthase ◽  
Neurological Manifestations ◽  
Biochemical Processes ◽  
B12 Deficiency ◽  
Spinal Degeneration ◽  
One Carbon Metabolism ◽  
And Function

A majority of patients with neurological disorders with chronic exposures to toxigenic molds and mycotoxins has vitamin B12 deficiency that is unrelated to dietary insufficiency. Vitamin B12 is a source of coenzymes, and participates in intracellular recycling of methionine, and in methionine synthase reactions. The biochemical processes that lead to B12 depletion and deficiency are not fully understood. This paper examines and assesses various most likely biochemical reasons that could impede upon the normal intracellular functions of vitamin B12 that lead to neurological manifestations. By biochemical implications and derivations, it is most likely that mycotoxins interrupt the structure and function of vitamin B12 through reactive interference with the normal One-Carbon metabolism leading to the observed clinical neurological manifestations such as nerve damage and, demyelination, degeneration of PNS leading to paralysis, progressive peripheral neuropathy, and spinal degeneration.

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.

Vitamin B12 Deficiency and West Syndrome: An Uncommon but Preventable Cause of Neurological Disorder. Report on Three Cases, One of Them with Late Onset during Vitamin B12 Treatment

2021 ◽  
Author(s):  
Piero Pavone ◽  
Federica Sullo ◽  
Raffaele Falsaperla ◽  
Filippo Greco ◽  
Agustina Crespo ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Late Onset ◽  
Vitamin B12 Deficiency ◽  
West Syndrome ◽  
Water Soluble ◽  
Vegan Diet ◽  
Inborn Errors ◽  
Water Soluble Vitamin ◽  
B12 Deficiency ◽  
Somatic Diseases

AbstractVitamin B12 is a water-soluble vitamin that plays a fundamental role as an essential cofactor for two enzymes responsible for the production of succinyl-CoA and methionine. Vitamin B12 deficiency can occur in infants and may be related to the breastfeeding mother's adherence to a vegan diet or somatic diseases in the mother. It should be differentiated from inborn errors of vitamin B12 metabolism. Herein, we report the cases of three infants with West syndrome; all three were breastfed by mothers who followed a strict vegan diet. In one of the three infants, West syndrome developed during treatment with vitamin B12 and normalization of the vitamin B12 level. Early treatment and replacement therapy are worthwhile to prevent serious neurological problems and to improve the patient's clinical course.

scholarly journals VITAMIN DEFICIENCY AND FOOD SUPPLEMENTS

2021 ◽  
Vol 9 (12) ◽  
pp. 540-552
Author(s):  
Saad Fahad Aldaihani
Keyword(s):  
Vitamin B12 ◽  
Human Body ◽  
Vitamin B12 Deficiency ◽  
Vitamin Deficiency ◽  
Megaloblastic Anaemia ◽  
Water Soluble ◽  
Vitamin B ◽  
B12 Deficiency ◽  
And Function ◽  
Harmful Effects

Vitamins are a heterogeneous group of organic compounds that help ensure the human bodys wellbeing and function. This paper introduces the importance of all vitamins, both water-soluble and fat-soluble, as well as problems deriving from their deficiency. Additionally, vitamin supplements as part of treating vitamin deficiency, and possible harmful effects on the human body areshowcased. The main focus of the paper is on the vitamin B complex, and vitamin B12 specifically. The benefits of vitamin B12, as well as its action in the human body and the noxious effects of any lack of vitamin B12 in the human body, are also discussed. Some of the health conditionsan individual may need to face when they have vitamin B12 deficiency include neural tube defects, Alzheimers disease, depression, and megaloblastic anaemia, which are also introduced and further discussed, in terms of symptomatology, causes and suggested treatment. The toxicity of vitamin B12 is also introduced, and possible causes for vitamin B12 deficiency are showcased.

scholarly journals A case report on hyperpigmentation in vitamin B12 deficiency

2019 ◽  
Vol 7 (5) ◽  
pp. 1944
Author(s):  
Vivek Kumar Verma ◽  
V. Vijayavarman
Keyword(s):  
Vitamin B12 ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Water Soluble ◽  
Animal Origin ◽  
Adequate Treatment ◽  
Cutaneous Manifestations ◽  
Food Of Animal Origin ◽  
Water Soluble Vitamin ◽  
B12 Deficiency

Cobalamin (Vitamin B12) is a water-soluble vitamin. Cobalamin is synthesized only by microorganisms. The only source of vitamin B12 for humans is food of animal origin. Hyperpigmentation of skin has been reported only rarely as the presenting manifestation of vitamin B12 deficiency. We report a patient who had hyperpigmentation as her presenting medical complaint and in whom Vitamin B12 deficiency was the cause.  A 36-year-old female presented with generalised weakness and progressive and asymptomatic hyperpigmentation of hand and feet for 5 months. She is vegetarian by diet. On examination, hyperpigmentation was present over dorsal aspect of metacarpophalangeal, proximal and distal interphalangeal joints. Hyperpigmentation were present over dorsum of the foot and over the joints. The tongue was depaillated, and hyperpigmentation was present. Her serum level of vitamin B12 was diminished (83pg/ml). Megaloblastic anemia presents with protean manifestations. The association between vitamin B12 deficiency and hyperpigmentation, although unusual, has been described. Cutaneous manifestations associated with B12 deficiency include characteristic mucocutaneous hyperpigmentation (most common), vitiligo, angular cheilitis, and hair-nail changes. It mainly affects knuckle pads and oral mucosa. It is an under-recognized sign of megaloblastic anemia and should always be looked for in the setting of pallor. Hyperpigmentation could be the earliest manifestation of vitamin B12 deficiency before anemia sets in. It is worthwhile to consider the possibility of vitamin B12 or folate deficiency in a patient with unexplained pigmentary changes. Early detection and adequate treatment will prevent anemia and various neurological manifestations.

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