The Effect of Vitamin B12 Deficiency on Methylfolate Metabolism and Pteroylpolyglutamate Synthesis in Human Cells

1974 ◽  
Vol 47 (6) ◽  
pp. 617-630
Author(s):  
A. Lavoie ◽  
E. Tripp ◽  
A. V. Hoffbrand
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Direct Effect ◽  
Vitamin B12 Deficiency ◽  
Pernicious Anaemia ◽  
Normal Subjects ◽  
Normal Cells ◽  
Methyl Group ◽  
Consistent Effect ◽  
B12 Deficiency

1. The uptake of 14C from [methyl-14C]methyItetrahydrofolate was significantly reduced in the phytohaemagglutinin (PHA)-stimulated lymphocytes from nine patients with untreated pernicious anaemia compared with the uptake in seven normal subjects. 2. The uptake of 14C from [14C]methyltetrahydrofolate by the lymphocytes from seven of the patients with pernicious anaemia was consistently increased by addition of vitamin B12in vitro. 3. The proportion of 14C taken up from [14C]methyltetrahydrofolate transferred to non-folate compounds was found to be significantly reduced in the PHA-stimulated lymphocytes from nine patients with untreated pernicious anaemia compared with the proportion transferred in the PHA-stimulated lymphocytes from seven normal subjects. Addition of vitamin B12in vitro consistently increased the transfer in vitamin B12-deficient cells but had no consistent effect in normal cells. 4. Normal and vitamin B12-deficient PHA-stimulated lymphocytes took up [3H]folic acid and after 72 h incubation converted this largely into pteroylpolyglutamate forms. 5. The proportion of labelled lymphocyte folate as pteroylpolyglutamate after incubation with [3H]folic acid was the same in vitamin B12-deficient as in normal lymphocytes and the proportion of pteroylpolyglutamates formed in vitamin B12-deficient lymphocytes was unaffected by addition of vitamin B12in vitro. 6. No radioactivity could be decteted in pteroylpolyglutamates after incubating normal PHA-stimulated lymphocytes with [14C]methyltetrahydrofolate for 72 h, suggesting that pteroylpolyglutamate forms of folate cannot be made directly from methyltetrahydrofolate. 7. These results are consistent with the ‘methyltetrahydrofolate trap’ hypothesis in vitamin B12 deficiency. It is suggested that reduced synthesis of pteroylpolyglutamates reported by others in vitamin B12-deficient cells may be secondary to the failure of removal of the methyl group from methyltetrahydrofolate rather than to a direct effect of vitamin B12 deficiency on the enzyme responsible for pteroylpolyglutamate synthesis. 8. Reduced entry of methyltetrahydrofolate into vitamin B12-deficient cells may be secondary to failure of conversion of this compound into tetrahydrofolate.

scholarly journals Differentiation between Vitamin B12—deficient and Folic Acid—deficient Megaloblastic Anemias with C14—Histidine

Blood ◽  
1963 ◽  
Vol 21 (4) ◽  
pp. 447-461 ◽  
Author(s):  
MATHEWS B. FISH ◽  
MYRON POLLYCOVE ◽  
THOMAS V. FEICHTMEIR
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Specific Activity ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Normal Subjects ◽  
Intermediary Metabolism ◽  
Folic Acid Deficiency ◽  
Acid Deficiency ◽  
B12 Deficiency

Abstract Intermediary metabolism of the monocarbon pool and histidine in normal subjects and patients with megaloblastic anemia was studied by continuous measurement of pulmonary excretion of C14O2 and urinary excretion of C14 after injection of L-histidine-2(ring)-C14. Cumulative pulmonary and renal excretion of C14 for 1 month by two normal subjects approximates 45 per cent of the amount injected. Within 4 months after injection of the dose used in this study, the resultant average tissue radiation decreases below the average natural terrestrial and cosmic radiation level. Simultaneous determination of two parameters, (1) cumulative 1-hour pulmonary C14 excretion and (2) the time of occurrence of maximum C14O2specific activity (Tmax), may permit rapid and unequivocal differentiation between folic acid deficiency and vitamin B12 deficiency in the pathogenesis of megaloblastic anemia. Folio acid deficiency results in marked diminution of pulmonary C14 excretion (approximately 0.1 per cent of injection C14 in 1 hour) and marked prolongation of C14O2-specific activity Tmax (approximately 3 hours), while both parameters are normal (approximately 1 per cent and less than 1 hour, respectively) in patients with vitamin B12 deficiency and megaloblastic anemia. Measurement during periods of reticulocyte response to either folio acid or vitamin B12 demonstrate normal C14O2-specific activity Tmax but decreased pulmonary C14 excretion. These observations suggest that prolongation of C14O2-specific activity Tmax is a sensitive index of folic acid deficiency or block and that if Tmax is normal, pulmonary C14 excretion is a sensitive index of the relative partition of the active monocarbon pool between pathways for oxidation and pathways for nucleic acid synthesis. This type of breath analysis seems to provide a quantitative dynamic representation of metabolic function which may be particularly useful in differentiating between the alterations of intermediary metabolism that occur in patients with folic acid-deficient megaloblastic anemia and in patients with vitamin B12-deficient megaloblastic anemia.

Chromatographic and Bioautographic Estimation of Plasma Cobalamins in Various Disturbances of Vitamin B12 Metabolism

1971 ◽  
Vol 40 (1) ◽  
pp. 1-16 ◽  
Author(s):  
J. C. Linnell ◽  
A. V. Hoffbrand ◽  
T. J. Peters ◽  
D. M. Matthews
Keyword(s):  
Vitamin B12 ◽  
Binding Capacity ◽  
Vitamin B12 Deficiency ◽  
Pernicious Anaemia ◽  
Normal Subjects ◽  
Visual Assessment ◽  
Solvent System ◽  
Parenteral Administration ◽  
Predominant Component ◽  
B12 Deficiency

1. This paper reports a survey of values for individual plasma cobalamins in normal subjects, hospital controls, and patients with vitamin B12 deficiency and diseases in which there are disturbances of B12 metabolism. The values were obtained by thin-layer chromatography and bioautography followed by photometric scanning or visual assessment. 2. Normal plasma contains methylcobalamin (the predominant component), deoxyadenosylcobalamin and hydroxocobalamin. The latter two compounds are not separable in the solvent system routinely used. In some samples there were traces of cyanocobalamin. The ratio of methylcobalamin to deoxyadenosylcobalamin plus hydroxocobalamin, normally greater than 1·0, was reduced in B12 deficiency. Many cases of untreated pernicious anaemia showed a high proportion (up to 40%) of cyanocobalamin. In folate deficiency there was no consistent change in individual cobalamins. Patients with leukaemias and liver disease showed a variety of changes, some attributable to alterations in plasma binding capacity and loss of deoxyadenosylcobalamin from the liver. 3. After oral or parenteral administration of cyanocobalamin, plasma cyanocobalamin increased and there was evidence of conversion to methylcobalamin. After parenteral administration of methylcobalamin, this compound increased in the plasma, but deoxyadenosylcobalamin plus hydroxocobalamin did not change. 4. Possible reasons for pathological changes in individual plasma cobalamins are discussed.

The Danger of B12 Deficiency in the Elderly

1998 ◽  
Vol 12 (4) ◽  
pp. 215-226 ◽  
Author(s):  
Margaret Wynn ◽  
Arthur Wynn
Keyword(s):  
Nervous System ◽  
Risk Factor ◽  
Heart Disease ◽  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Pernicious Anaemia ◽  
The Elderly ◽  
Nerve Cells ◽  
Accelerated Ageing ◽  
B12 Deficiency

Vitamin B12 deficiency damages nerve cells and aggravates nervous system disorders even in the absence of evidence of anaemia. Prevalence of B12 deficiency increases with age especially over 65 and is frequently associated with Alzheimer's disease. Recent American surveys record a higher prevalence of B12 deficiency and of undiagnosed and untreated pernicious anaemia in the elderly than reported earlier. B12 deficiency is also reported to be a risk factor for heart disease, stroke and accelerated ageing.

scholarly journals Prevalence of Iron, Folic Acid and Vitamin B12 Deficiency in Patients with Thalassemia Minor

2013 ◽  
Vol 7 (4) ◽  
pp. 83 ◽  
Author(s):  
Suheyl Asma ◽  
Cigdem Gereklioglu ◽  
Ahmet Erdogan ◽  
Mahmut Yeral ◽  
Mutlu Kasar ◽  
...  
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Thalassemia Minor ◽  
B12 Deficiency ◽  
Iron Folic Acid

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.

scholarly journals Helicobacter pylori associated vitamin B12 deficiency, pernicious anaemia and subacute combined degeneration of the spinal cord

2013 ◽  
Vol 2013 (sep29 1) ◽  
pp. bcr2013200380-bcr2013200380 ◽  
Author(s):  
H. B. Gowdappa ◽  
M. Mahesh ◽  
K. V. K. S. N. Murthy ◽  
M. G. Narahari
Keyword(s):  
Spinal Cord ◽  
Helicobacter Pylori ◽  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Pernicious Anaemia ◽  
Subacute Combined Degeneration ◽  
B12 Deficiency

scholarly journals Effect of vitamin B12 and folic acid deficiencies on neutrophil function

Blood ◽  
1976 ◽  
Vol 47 (5) ◽  
pp. 801-805 ◽  
Author(s):  
SS Kaplan ◽  
RE Basford
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Cell Function ◽  
Vitamin B12 Deficiency ◽  
Folic Acid Deficiency ◽  
Specific Therapy ◽  
Bacterial Killing ◽  
Leukocyte Function ◽  
Acid Deficiency ◽  
B12 Deficiency

Abstract Morphological and quantitative neutrophil abnormalities are common in the megaloblastic anemias of vitamin B12 and folic acid deficiency. Little is known, however, about the role of these vitamins in normal leukocyte function. Seven patients with megaloblastic bone marrows, four with vitamin B12 deficiency and three with folic acid deficiency, were studied to determine the effect, if any, of these deficiencies on leukocyte function. Phagocytosis of staphylococci, hexose monophosphate shunt activation with phagocytosis, and microbicidal capacity against Staphylococcus aureus were determined prior to the institution of specific therapy. In two instances, these studies were repeated following treatment. There was no impairment of phagocytosis per se, and resting metabolism was not significantly decreased. With phagocytosis, however, metabolic activation was decreased to 35%-36% of control values in the leukocytes of patients with vitamin B12 deficiency but not in the leukocytes of patients with folic acid deficiency. Bacterial killing was slightly decreased in vitamin B12 but not in folic acid deficiency. These abnormalities of function were reversed after specific therapy. These findings suggested a specific role for vitamin B12 in the production of intermediates necessary for normal cell function.

Vitamin B12 and folic acid associated megaloblastic anemia: Could it mislead the diagnosis of breast cancer?

2019 ◽  
Vol 89 (5-6) ◽  
pp. 255-260
Author(s):  
Inanc Karakoyun ◽  
Can Duman ◽  
Fatma Demet Arslan ◽  
Anil Baysoy ◽  
Banu Isbilen Basok
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
Vitamin B12 ◽  
Megaloblastic Anemia ◽  
Vitamin B12 Deficiency ◽  
Normal Group ◽  
Ca 125 ◽  
Folic Acid Deficiency ◽  
Acid Deficiency ◽  
B12 Deficiency

Abstract. CA 15-3 is a tumor-associated antigen and is overexpressed in breast tumors, and may also be high in some other non-cancerous conditions. The aim of this study was to investigate the effect of megaloblastic anemia due to vitamin B12 or folic acid deficiency on the levels of tumor markers. Five-year patient data were retrospectively analyzed. The associations between megaloblastic anemia due to vitamin B12 deficiency and CA 15-3, CA 125, CA 19-9, CEA, and AFP levels were analyzed. Furthermore, association between CA 15-3 level and megaloblastic anemia due to folic acid deficiency was evaluated. Median CA 15-3 level was 38.1 U/mL in the group with megaloblastic anemia due to vitamin B12 deficiency(n = 15), 46.7 U/mL in the group with megaloblastic anemia related to folic acid deficiency (n = 3), and 17.8 U/mL in the normal group(n = 1724). CA 15-3 levels were significantly higher among patients with vitamin B12- and folic acid-associated megaloblastic anemia compared to the normal group (p = 0.001 and p = 0.005, respectively). Megaloblastic anemia due to vitamin B12 deficiency was not associated with any significant differences in CA 125, CA 19-9, CEA, or AFP levels compared to the normal group (p = 0.777, p = 0.327, p = 0.577, and p = 0.197, respectively). The numbers of anemic and normal subjects compared in these tests were 12 vs. 1501, 17 vs. 1827, 4 vs. 897, and 8 vs. 1041, respectively. In conclusion, megaloblastic anemia results in ineffective erythropoiesis, and increased levels of CA 15-3 may be associated with this issue. Clinicians should take this into account when evaluating for a pre-diagnosis of breast cancer.

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