scholarly journals The effect of folate analogues and vitamin B12 on provision of thymine nucleotides for DNA synthesis in megaloblastic anemia

Blood ◽  
1982 ◽  
Vol 59 (3) ◽  
pp. 634-640
Author(s):  
MR Taheri ◽  
RG Wickremasinghe ◽  
BF Jackson ◽  
AV Hoffbrand
Keyword(s):  
Vitamin B12 ◽  
De Novo ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Folate Deficiency ◽  
Minor Role ◽  
B12 Deficiency ◽  
Thymidylate Synthesis ◽  
Marrow Cells

The role of vitamin B12 in the folate dependent biosynthesis of thymidine nucleotides is controversial. In an attempt to clarify this, three methods have been used to assess the relative efficacy of vitamin B12 (hydroxocobalamin) and various folate analogues in titrated concentrations at correcting ‘de novo’ thymidylate synthesis by megaloblastic human marrow cells: (1) The deoxyuridine (dU) suppression test which analyses the reduction in (3H)-thymidine labeling of DNA by unlabeled dU. Marrow cells were also labeled with (6–3H)-dU with assessment of (2) its incorporation into DNA and (3) the accumulation of (6–3H)-deoxyuridine monophosphate (3H-dUMP). The three methods gave similar results. In both, N6-formyl tetrahydrofolate (formyl-FH4) was the most effective agent at correcting thymidylate synthesis in megaloblastic anemia due to vitamin B12 or folate deficiency. Vitamin B12 corrected the lesion in vitamin B12 deficiency but not in folate deficiency. Tetrahydrofolate (FH4) and folic acid were effective in deficiency of vitamin B12 or folate, although in both deficiencies they were less effective than formyl-FH4. Methyl-FH4 was effective in folate deficiency but not in vitamin B12 deficiency. These results confirm the failure of methyl-FH4 utilisation in vitamin B12 deficiency. They suggest that if vitamin B12 is needed in the formylation of FH4, this is a minor role in provision of the correct coenzyme for thymidylate synthesis compared with its major role of provision of FH4 from methyl- FH4.

scholarly journals The effect of folate analogues and vitamin B12 on provision of thymine nucleotides for DNA synthesis in megaloblastic anemia

Blood ◽  
1982 ◽  
Vol 59 (3) ◽  
pp. 634-640 ◽  
Author(s):  
MR Taheri ◽  
RG Wickremasinghe ◽  
BF Jackson ◽  
AV Hoffbrand
Keyword(s):  
Vitamin B12 ◽  
De Novo ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Folate Deficiency ◽  
Minor Role ◽  
B12 Deficiency ◽  
Thymidylate Synthesis ◽  
Marrow Cells

Abstract The role of vitamin B12 in the folate dependent biosynthesis of thymidine nucleotides is controversial. In an attempt to clarify this, three methods have been used to assess the relative efficacy of vitamin B12 (hydroxocobalamin) and various folate analogues in titrated concentrations at correcting ‘de novo’ thymidylate synthesis by megaloblastic human marrow cells: (1) The deoxyuridine (dU) suppression test which analyses the reduction in (3H)-thymidine labeling of DNA by unlabeled dU. Marrow cells were also labeled with (6–3H)-dU with assessment of (2) its incorporation into DNA and (3) the accumulation of (6–3H)-deoxyuridine monophosphate (3H-dUMP). The three methods gave similar results. In both, N6-formyl tetrahydrofolate (formyl-FH4) was the most effective agent at correcting thymidylate synthesis in megaloblastic anemia due to vitamin B12 or folate deficiency. Vitamin B12 corrected the lesion in vitamin B12 deficiency but not in folate deficiency. Tetrahydrofolate (FH4) and folic acid were effective in deficiency of vitamin B12 or folate, although in both deficiencies they were less effective than formyl-FH4. Methyl-FH4 was effective in folate deficiency but not in vitamin B12 deficiency. These results confirm the failure of methyl-FH4 utilisation in vitamin B12 deficiency. They suggest that if vitamin B12 is needed in the formylation of FH4, this is a minor role in provision of the correct coenzyme for thymidylate synthesis compared with its major role of provision of FH4 from methyl- FH4.

scholarly journals 5-Methyltetrahydrofolate related enzymes and DNA polymerase alpha activities in bone marrow cells from patients with vitamin B12 deficient megaloblastic anemia

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 832-837
Author(s):  
Y Kano ◽  
S Sakamoto ◽  
K Hida ◽  
K Suda ◽  
F Takaku
Keyword(s):  
Bone Marrow ◽  
Vitamin B12 ◽  
Dna Polymerase ◽  
Methylenetetrahydrofolate Reductase ◽  
Bone Marrow Cells ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Dna Polymerase Alpha ◽  
B12 Deficiency ◽  
Marrow Cells

The activities of 5-methyltetrahydrofolate (5-CH3THF) related enzymes and DNA polymerase alpha were determined in bone marrow cells obtained from patients with vitamin B12 deficient megaloblastic anemia and compared with those from healthy volunteers and patients with hemolytic anemia. 5-CH3THF homocysteine methyltransferase activity was significantly lower than that in the control subjects. 5,10- methylenetetrahydrofolate reductase activity was only slightly elevated to that in the control subjects. DNA polymerase alpha activity was significantly higher than that in the control. High deoxyuridine suppression test values in vitamin B12 deficient bone marrow cells were improved by tetrahydrofolate, but not by 5-CH3THF. These data indicate that, even though the reverse reaction catalyzed by 5,10- methylenetetrahydrofolate reductase may be operative in vitamin B12 deficiency, it is not sufficient to correct the disturbance in folate metabolism in vitamin B12 deficiency. Increased DNA polymerase alpha activity may be due to compensation for disarranged DNA synthesis.

scholarly journals 5-Methyltetrahydrofolate related enzymes and DNA polymerase alpha activities in bone marrow cells from patients with vitamin B12 deficient megaloblastic anemia

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 832-837 ◽  
Author(s):  
Y Kano ◽  
S Sakamoto ◽  
K Hida ◽  
K Suda ◽  
F Takaku
Keyword(s):  
Bone Marrow ◽  
Vitamin B12 ◽  
Dna Polymerase ◽  
Methylenetetrahydrofolate Reductase ◽  
Bone Marrow Cells ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Dna Polymerase Alpha ◽  
B12 Deficiency ◽  
Marrow Cells

Abstract The activities of 5-methyltetrahydrofolate (5-CH3THF) related enzymes and DNA polymerase alpha were determined in bone marrow cells obtained from patients with vitamin B12 deficient megaloblastic anemia and compared with those from healthy volunteers and patients with hemolytic anemia. 5-CH3THF homocysteine methyltransferase activity was significantly lower than that in the control subjects. 5,10- methylenetetrahydrofolate reductase activity was only slightly elevated to that in the control subjects. DNA polymerase alpha activity was significantly higher than that in the control. High deoxyuridine suppression test values in vitamin B12 deficient bone marrow cells were improved by tetrahydrofolate, but not by 5-CH3THF. These data indicate that, even though the reverse reaction catalyzed by 5,10- methylenetetrahydrofolate reductase may be operative in vitamin B12 deficiency, it is not sufficient to correct the disturbance in folate metabolism in vitamin B12 deficiency. Increased DNA polymerase alpha activity may be due to compensation for disarranged DNA synthesis.

scholarly journals Tropical sprue in megaloblastic anemia

2017 ◽  
Vol 5 (9) ◽  
pp. 4133 ◽  
Author(s):  
Yoganathan Chidambaram ◽  
Anith Kumar Mambatta ◽  
Sujith K. Sivaraj
Keyword(s):  
Bone Marrow ◽  
Vitamin B12 ◽  
Megaloblastic Anemia ◽  
Macrocytic Anemia ◽  
Vitamin B12 Deficiency ◽  
Folate Deficiency ◽  
Duodenal Biopsy ◽  
Tropical Sprue ◽  
Geographical Regions ◽  
B12 Deficiency

Background: The causes of megaloblastic anemia may vary in different geographical regions. The aim of the present study is to evaluate the utilization of bone marrow examination and upper gastrointestinal endoscopy (UGIE) in megaloblastic anemia.Methods: This was a cross-sectional descriptive study done on 50 patients (age ≥15years) of macrocytic anemia after applying inclusion and exclusion criteria. A bone marrow aspiration with biopsy and an UGIE with duodenal biopsy were performed in consented patients with evidence of megaloblastic anemia in the peripheral smear or Vitamin B12 deficiency or folate deficiency or both.Results: Out of 50 cases, 38 patients had pure Vitamin B12 deficiency, 2 patients had pure folate deficiency and 5 patients had combined deficiency. Among 43 patients with vitamin B12 deficiency, only four (9.3%) were vegetarians and remaining 39 (90.7%) were having non-vegetarian diet. Bone marrow study was done in 29 patients (out of 50) and all of them were found to have megaloblastic erythropoiesis in the bone marrow. Thirty three out of 50 consented for UGIE and duodenal biopsy. Out of 33, 17 patients (51.5%) had features of tropical sprue in biopsy.Conclusions: We found a high prevalence of tropical sprue in megaloblastic anemia due to Vitamin B12 and/or folate deficiency. We recommend that UGIE with deep duodenal biopsy should be considered in all patients with megaloblastic anemia to rule out tropical sprue in India.

scholarly journals The prevalence of low serum levels of Vitamin D, Vitamin B12, folate and ferritin in adolescents: Single center experience

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110076
Author(s):  
Nazmi Mutlu Karakaş
Keyword(s):  
Vitamin D ◽  
Vitamin B12 ◽  
Medical Records ◽  
Vitamin B12 Deficiency ◽  
Serum Levels ◽  
Folate Deficiency ◽  
Well Child Care ◽  
Single Center Experience ◽  
B12 Deficiency ◽  
Prevalence Of Anemia

Background: In this study, the aim was to evaluate the prevalence of vitamin D, vitamin B12, ferritin, and folate deficiencies in adolescence to clarify the need for early diagnosis and therapy. Methods: The medical records of adolescents between 10 and 18 years of age between 01 September 2018 and 28 February 2019 as healthy with non-specific complaints, or due to well-child care visits, were analyzed retrospectively. Results: A total of 1847/2507 (73.6%) adolescents were included in the study. The prevalence of vitamin D deficiency was 25.7% (n: 178/691). Vitamin B12 deficiency prevalence was 69.2% (n: 753/1088). The prevalence of anemia and ferritin deficiency was 4.8% and 13.26%. The prevalence of folate deficiency was 37.9% (n: 413/1088). VDD prevalence was statistically significantly higher in females than males (F/M:116/62). VB12D prevalence, the number and mean age of females with hemoglobin deficiency, and low ferritin levels was found to be statistically significantly higher in females than males. Conclusions: The prevalence of vitamin D, vitamin B12, folate deficiency and low ferritin levels was found to be high among adolescents. In particular, adolescents admitting with non-specific complaints and for control purposes in big cities must be considered to be at risk for the deficiency of these vitamins and low level of ferritin.

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 EFEK FORTIFIKASI VITAMIN B12 TERHADAP KADAR VITAMIN B12 SERUM DAN HOMOSISTEIN SERUM PADA VEGETARIAN

2020 ◽  
Vol 11 (1) ◽  
pp. 114-120
Author(s):  
Susianto Susianto
Keyword(s):  
Vitamin B12 ◽  
Homocysteine Level ◽  
Megaloblastic Anemia ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
Natural Sources ◽  
Serum Homocysteine ◽  
Microparticle Enzyme Immunoassay ◽  
B12 Deficiency ◽  
Community Trial

Introduction: Vegetarians consume plant-based foods with or without eggs and milk. Vegetarians are at risk of vitamin B12 deficiency, as natural sources of vitamin B12 are limited to animal-based foods. Vitamin B12 deficiency can lead to megaloblastic anemia, nerve damage and increase homocysteine level. Higher homocysteine level can increase the risk of coronary heart disease and stroke. The objective of this study was to investigate the effect of vitamin B12 fortification on the level of serum vitamin B12 and homocysteine in vegetarian. Method: The research design was an experimental study, community trial. The samples were 42 vegetarians with vitamin B12 deficiency (< 156 pmol/L) selected from 118 vegetarians as members of Indonesia Vegetarian Society (IVS) Pekanbaru, treated by vitamin B12 fortified oatmeal for three months from March to June 2010.  Serum vitamin B12 and homocysteine were measured by electrochemiluminescent immunoassay and microparticle enzyme immunoassay method respectively. Result: Prevalence of vitamin B12 deficiency in vegetarian was 35.6%. Statistical analysis showed a significant increase of serum vitamin B12 from 124.6 to 284.6 pmol/L (p=0.001) and significant decrease of serum homocysteine from 20.1 to 15.1 µmol/L (p=0.001). Conclusion: Consumption of vitamin B12 fortified oatmeal increases the level of serum vitamin B12 and decreases the level of serum homocysteine significantly in vegetarian with vitamin B12 deficiency.

scholarly journals Hematologic Manifestations of Vitamin B12 Deficiency in Swine

Blood ◽  
1951 ◽  
Vol 6 (10) ◽  
pp. 867-891 ◽  
Author(s):  
G. E. CARTWRIGHT ◽  
BETTY TATTING ◽  
JEAN ROBINSON ◽  
N. M. FELLOWS ◽  
F. D. GUNN ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vitamin B12 ◽  
Liver Damage ◽  
Megaloblastic Anemia ◽  
Macrocytic Anemia ◽  
Vitamin B12 Deficiency ◽  
Deficiency Anemia ◽  
Severe Neutropenia ◽  
Pteroylglutamic Acid ◽  
B12 Deficiency

Abstract In an effort to produce a deficiency of vitamin B12 a total of 70 pigs were fed a purified diet containing soybean alpha protein in place of casein. One group of animals was started on the diet at 2 to 7 days of age. A second group began at 21 to 28 days of age. Methionine, iodinate casein, desiccated thyroid and pteroylglutamic acid were added to the diet of certain animals and! omitted from the diet of other pigs. In addition, 9 pigs were gastrectomized. Forty-three of the animals survived for a sufficiently long period of time for adequate evaluation of the results of the experiment. Severe liver damage was observed in 24 of the 25 animals autopsied. The only animal not showing liver damage received vitamin B12 from the beginning of the experiment. Necrosis of the liver cells, fatty infiltration, or both, occurred in the presence of a high fat diet containing apparently adequate amounts of protein, choline, vitamin E and methionine. These pathologic changes were apparently prevented but not reversed by the administration of vitamin B12. Growth of the animals on the above diets without added vitamin B12 was retarded as compared with the growth of animals on the same diet supplemented with this vitamin. The administration of vitamin B12 to the deficient animals resulted in rapid growth. Of the 39 animals not receiving vitamin B12 13 failed to develop anemia, 16 developed a mild anemia and in 10 a moderately severe anemia was present. When present the anemia was normocytic and in 24 pigs was accompanied by a moderately severe neutropenia. Differential cell counts on the sternal marrow were normal except for a slight increase in the proportion of normoblasts. These hematologic alterations were neither consistently or completely corrected by the administration of vitamin B12 in spite of the fact that definite and sometimes marked reticulocyte increases followed. When methionine deficiency was associated with vitamin B12 deficiency, anemia appeared to be more severe. The administration of aureomycin, an "animal protein factor," did not stimulate growth and failed to induce a hemopoietic response. There was no macrocytic anemia, the bone marrow was not megaloblastic, and neurologic disturbances or morphologic alterations in the neutrophils were not observed. These results are in contrast to those obtained in pigs with an experimentally produced deficiency of pteroylglutamic acid. Such animals develop macrocytic anemia, leukopenia and a macronormoblastic type of bone marrow. It is not possible to give with any assurance the reason why megaloblastic anemia was not produced in the "B12-deficient" animals. This may have been due to the fact that (1) the deficiency was not sufficiently severe to result in such a change in the hemopoietic system; or (2) because pteroylglutamic acid prevents the development of megaloblastic anemia even in the absence of vitamin B12.

Brief Report: Observations on Conjugated and Unconjugated Blood Folate Levels in Megaloblastic Anemia and the Effects of Vitamin B12

Blood ◽  
1965 ◽  
Vol 26 (3) ◽  
pp. 354-359 ◽  
Author(s):  
K. N. JEEJEEBHOY ◽  
S. M. PATHARE ◽  
J. M. NORONHA
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Cellular Level ◽  
B12 Deficiency

Abstract Vitamin B12 deficiency was associated with a rise in unconjugated folates and marked depletion of intracellular conjugated folates. The changes could be reversed by giving vitamin B12. These results probably indicate a way by which vitamin B12 and folic acid are interrelated at the cellular level.

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