Role Of Vitamin B12 Research Articles

Role of vitamin B12 and folate deficiencies in carcinogenesis.

A significant body of experimental evidence supports the notion that a deficiency of either vitamin B12 or folic acid enhances the activity of various carcinogens. Unifying mechanisms are proposed to explain this cocarcinogenic role.

The role of vitamin B12 and folate in carcinogenesis.

The roles of vitamin B12 and folate in carcinogenesis are largely extensions of and linked to their roles in normal metabolism, particularly 1-carbon unit metabolism. A possible key area may be hypomethylation to "switch on" genes and methylation to "switch them off." Some vitamin analogues may act as antivitamins in these reactions, as may some vitamin-binding proteins. Others may act as specific delivery proteins. Using appropriate radioactive substrates and suspensions of vitamin-dependent normal and malignant cells, it may be possible to work out their positive and negative control of DNA synthesis.

The Effect of Folate Analogues and Vitamin B12 on Provision of Thymine Nucleotides for DNA Synthesis in Megaloblastic Anemia

AbstractThe role of vitamin B12 in the folate dependent biosynthesis of thymine 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, NB-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.

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

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.

Neurobiology of Pyridoxine.

There has been a continuing interest in the role of pyridoxine (vitamin B6) in maintenance of the structure and function of the nervous system. At the International Symposium (Harris et al., 1964) on vitamin B6 in honor of Professor Paul Gyorgy, Roberts et al. (1964) mentioned that “γ-amino butyric acid (GABA) plays an inhibitory or modulatory role in the central nervous sytem (CNS).” Since then, more direct evidence has accumulated to confirm both a neurotransmitter role for GABA in the vertebrate CNS and the regulation of its synthesis by pyridoxal phosphate (PALP).

Vitamin B6 in the Etiology of Gizzard Erosion in Growing Chickens

Six experiments have been completed on day-old male cross-bred chicks for periods of up to 2 and 4 weeks to learn more about the role of pyridoxine in the etiology of gizzard erosion. At the end of each experiment, chicks were sacrificed and their gizzards removed and scored for the severity and incidence of erosion. The results of these experiments confirm the previous finding that the severity and incidence of gizzard erosion is increased by B6 deficiency. They further show that taurocholic acid, at 1% of the diet, had a protective effect against this erosion. Feeding B6 -adequate rations to chicks that previously had been fed a B6-deficient diet led to partial healing of gizzard erosions. Results also indicate that the feeding of purified diets to growing chickens produces a higher incidence of erosion than that of practical-type diets. Texture of the diet did not influence the incidence of the erosion, because grinding a practical diet to the same fineness as a purified diet did not increase gizzard erosion. Pair-feeding experiments showed that gizzard erosion in partially starved chicks was not a specific result of anorexia but of deficiencies in certain nutrients, one of which is vitamin B6.

Depression and oral contraceptives: the role of pyridoxine

Comploment (Napp Laboratories Ltd) contains pyridoxine hydrochloride, 100 mg, in a controlled-release base, and is promoted to counteract depression associated with the contraceptive pill. What is the evidence for this claimed indication?

320. Role of pyridoxine in the steroid regulated uptake of catecholamines

320. Role of pyridoxine in the steroid regulated uptake of catecholamines

Role of pyridoxine in the metabolism of putrescine in the rat.

1. The ability of rats to metabolize radioactive putrescine to 14CO2 in vivo has been studied. 2. Animals made deficient in pyridoxine exhibit a significantly lower rate of catabolism of the diamine. 3. There dose not appear to be an important interaction between the effects of the deficiency and those stemming from treatment of the animals with the diamine oxidase inhibitor aminoguanidine. 4. These results favour the concept of a role of pyridoxal cofactor in the metabolism of diamines, presumably at the diamine oxidase stage.

Role of vitamin B12 and enzymes related to methylmalonyl-CoA mutase in a methanol-utilizing bacterium, Protaminobacter ruber.

A methanol-utilizing bacterium, Protaminobacter ruber, required cobalt ion or vitamin B12 as its growth factor, which could be replaced by succinate among various additions to the cobalt-deficient medium. The presence of adenosylcobalamin (adenosyl-B12)-dependent methylmalonyl-coenzyme A (CoA) mutase was demonstrated in the cell-free extracts of P. ruber. The specific activity of this mutase was not only fairly high in comparison with that reported with other organisms but also detected at a similar level throughout the cultivation period. The cell-free extracts of P. ruber grown on non-C1 compounds as a sole carbon and energy source also had methylmalonyl-CoA mutase activity. Furthermore, the extracts of this microorganism catalyzed the reactions from propionyl-CoA to succinyl-CoA and from alpha-ketoglutarate to alpha-hydroxyglutarate.

Pyridoxine and atherosclerosis: role of pyridoxine in the metabolism of lipids and glycosaminoglycans in rats fed normal and high fat, high cholesterol diets containing 16% casein.

The effect of administration of low and high doses of pyridoxine on the metabolism of lipids and glycosaminoglycans has been studied in rats fed normal and high fat, high cholesterol diets. Low doses of pyridoxine (0.005 mg/100 g body weight) caused increased concentrations, of cholesterol and triglycerides in the serum and aorta in animals fed normal and high fat, high cholesterol diets. Administration of high doses of pyridoxine (5.0 mg/100 g body weight) caused decrease in the concentration of these lipids in these tissues except in the case of the aorta in the animals fed a normal diet. Low doses of pyridoxine generally caused a decrease in the concentration of many glycosaminoglycan fractions in the aorta in rats fed normal and high fat, high cholesterol diets, whilst high doses caused an increase. The activity of glucosaminephosphate isomerase (glutamine-forming) and UDPglucose dehydrogenase, both key enzymes in the biosynthetic pathway of glycosaminoglycans, decreased in rats given low doses of pyridoxine and increased in rats given high doses. The activity of many enzymes concerned with degradation of glycosaminoglycans--hyaluronoglucosidase, beta-glucuronidase, beta-N-acetylglucosaminidase, aryl sulphatase, and cathepsin D--generally increased in rats fed low doses of the pyridoxine and decreased in those given high doses. The concentration of hepatic 3'-phosphoadenosine-5'-phosphosulphate, and the activity of the sulphate-activating system and of aryl sulphotransferase decreased when the dose of pyridoxine was low and increased when the dose was high.

Role of vitamin B12 in the reduction of ribonucleotides into deoxyribonucleotides in Drosophila cells grown in vitro

Adenosine was found to inhibit growth of Drosophila melanogaster cells in culture. This toxic effect is prevented by the addition of uridine + deoxyuridine, or uridine + deoxycytidine. In the presence of vitamin B12, uridine alone is sufficient to sustain proliferation of Drosophila cells inhibited by adenosine. Moreover, vitamin B12 increases the incorporation of [3H] uridine into DNA, and decreases the incorporation of [3H] thymidine. No modification of the incorporation of [14C] adenine, [14C] adenonsine or [3H] cytosine into DNA could be found in the presence of vitamin B12. It is concluded that vitamin B12 is involved in an enhanced conversion of uridine ribonucleotides into deoxyribonucleotides derived from uridine.

Effect of vitamin B12 and folic acid deficiencies on neutrophil function

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.

Role of vitamin B6 on leucine-induced metabolic changes.

Administration of leucine at 3% level in the diet has been shown to increase tryptophan oxygenase activity and to decrease kynureninase activity in the liver and to increase quinolinic acid excretion in the urine of rats fed low amounts of vitamin B6 (0.5 mug/g diet). Vitamin B6 at 3 mug/g of diet was able to reverse the effects of leucine on enzyme activities, but not on quinolinic acid excretion. Isoleucine at 0.2% level could counteract the leucine effect on kynureninase but not on tryptophan oxygenase. Administration of leucine also decreased the 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain. Simultaneous administration of isoleucine could counteract the effects of leucine on brain 5-HT and 5-HIAA partially at low amount of vitamin B6 but completely at higher levels of vitamin B6 in the diet.

Hookworm anaemia and intestinal malabsorption associated with hookworm infestation.

Anaemia in hookworm infestation due to iron deficiency has been firmly established [1,2]. Blood loss in these patients [3–8] is associated quantitatively with hookworm load. Protein loss in patients with severe hookworm infestation may lower the total serum protein [6, 9]. Haemopoietic nutrients other than these, namely vitamin B12 and folic acid, however, need to be examined. A variable proportion of patients with hookworm disease have functional and structural changes of the small bowel leading to the clinical features of malabsorption [10–15]. Earlier studies have suggested that in humans, protein deficiency is related to abnormalities of small intestine function and structure [16, 17]. Reversal of malabsorption in cases with or without hookworm infestation on a high protein diet without any additional vitamin, antibiotic and without dewormification in the former has been demonstrated [17, 18]. It has also been postulated that vitamin B12 deficiency may either induce or aggravate the intestinal malabsorption [19]. The present communication comments on anaemia, haemopoietic nutrient deficiency and protein deficiency in patients with hookworm infestation. It also discusses the role of vitamin B12 and protein deficiency in the etiopathogenesis of intestinal malabsorption. Further, similar studies have been also carried out in patients without hookworm infestation and a comparison of the two has been made.

Depression induced by oral contraception and the role of vitamin B6 in its management.

Depression induced by oral contraceptives (OCs and the role of Vitamin-B6 in its management were presented. Approximately 1 in 15 women taking OCs develop induced pharmacological depression which may be related to an upset in tryptophan metabolism which is shunted from the 5-hydroxytryptamine pathway to the kynurine pathway. The depression in those women with an absolute Vitamin-B6 deficiency may be suppressed by vitamin-B6 therapy. Laboratory confirmation at present is not practical; therefore it is suggested that a daily dose of 50 mg Vitamin-B6 be given to all women with depressive symptoms while taking OCs.

Delayed maturation of the renal cortex in the vitamin B6-deficient newborn rat.

Extract: Retarded growth, lethargy, motor retardation, and tremor were observed in all offspring from dams subjected to vitamin B6 deficiency during pregnancy or shortly after delivery of litters. Renal development in these animals was delayed and the degree of retardation depended upon the time of initiation of the deficient diet. Uremia, lethargy, motor retardation, and tremor coincided with this maturational delay. The degree of reduction of vitamin B6 in liver and brain bore no systematic relation to the degree of deprivation. Moreover, all symptoms were consistent with the effects of uremia alone. Although cellular mitotic rates were clearly decreased in deprived animals, there was no apparent failure of glomerular neogenesis from diverse vascular, tubular, and subcapsular cellular components.Speculation: Retarded growth, lethargy, motor retardation, and tremor, observed in vitamin B6-deficient young, were the secondary consequences of uremia which resulted from retarded renal development. This suggests a possible role of vitamin B6 in kidney morphogenesis.

Alkyl–cobalt mediation of DDT hydrolysis

A POSSIBLE role for vitamin B12 in the detoxification of polyhalogenated hydrocarbon pesticides such as DDT has occasionally been postulated (ref 1 and references therein), and DDT has been shown to inhibit bacterial B12-dependent methanogenesis2. Although reduced cobalamins and cobaloximes will react with simpler species such as polyhalomethanes3,4, no adduct between DDT or related compounds and cobalt has previously been observed2. It has been suggested that alkyl–cobalt complexes of the ligand CR (Fig. 1) have some chemical similarities to B12 (ref. 5) and zinc complexes of CR have yielded results relevant to carbonic anhydrase6. We report the use of cobalt–CR to mediate the hydrolysis of DDT, the isolation of an alkyl–cobalt derivative of a hydrolysis product of DDT, and the formation of di(p-chlorophenyl) ketone from this compound.

Role of Vitamin B6 in Neurobiology. M. S. Ebadi and E. Costa, Eds. Raven Press, Hewlett, Long Island, N. Y. 11557, 1972, x + 238 pp. $15.95

Role of Vitamin B6 in Neurobiology. M. S. Ebadi and E. Costa, Eds. Raven Press, Hewlett, Long Island, N. Y. 11557, 1972, x + 238 pp. $15.95

Developments leading to the metabolic ce:role of vitamin B6

Developments leading to the metabolic ce:role of vitamin B6