1975
DOI: 10.1007/bf01732201
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The relationships between vitamin B12 and folic acid and the effect of methionine on folate metabolism

Abstract: The relationship between vitamin B12 and folate and the effect of methionine on folate metabolism during B12 deficiency in rats is best explained by the prevention of the accumulation of 5-methyl-H4PteGlu by vitamin B12 and/or methionine. Although several points remain to be clarified, the 'methyl trap' hypothesis provides the most satisfactory explanation for the relation between vitamin B12, methionine and folic acid. This concept is extended by the hypothesis that H4PteGlu is the most active substrate for p… Show more

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Cited by 40 publications
(19 citation statements)
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“…The protective effect of methionine during exposure to nitrous oxide is attributed to its conversion into Sadenosylmethionine. This compound could act by several mechanisms but mainly by (1) an inhibition of 5,10-methylene-THF reductase associated with a stimulation of methionine synthetase, thus alleviating the trapping of folate [26,27]; (2) an enhancement of the methylation reactions that require S-adenosylmethionine as a methyl donor [15]. The favourable effect of methionine in our patient is probably due to a stimulation of the methylation reactions in the brain.…”
Section: Low Normal Plasma Methionine and Presence Of Cystathionine Imentioning
confidence: 85%
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“…The protective effect of methionine during exposure to nitrous oxide is attributed to its conversion into Sadenosylmethionine. This compound could act by several mechanisms but mainly by (1) an inhibition of 5,10-methylene-THF reductase associated with a stimulation of methionine synthetase, thus alleviating the trapping of folate [26,27]; (2) an enhancement of the methylation reactions that require S-adenosylmethionine as a methyl donor [15]. The favourable effect of methionine in our patient is probably due to a stimulation of the methylation reactions in the brain.…”
Section: Low Normal Plasma Methionine and Presence Of Cystathionine Imentioning
confidence: 85%
“…4): the methylcobalamin-dependent enzyme, methionine synthetase, (reaction 1) utilises 5-methyl-THF to form methionine from homocysteine; as said before, this reaction is also required to allow 5-methyl-THF, the plasma form of folate, to be converted into folate polyglutamates; methionine adenosyltransferase (reaction 2) converts methionine into S-adenosylmethionine (SAM), a high-energy compound that functions as the methyl donor in a series of vital methylating reactions, including the methylation of myelin in the brain. By inhibiting the irreversible reduction of 5,10-methylene-THF into 5-methyl-THF, catalysed by 5,10-methylene-THF reductase (reaction 3), and by stimulating methionine synthetase (see [27] and references therein), Sadenosylmethionine also avoids the trapping of THF in the form of 5-methyl-THF and allows its recycling and utilisation by the other reactions that require single carbon units. The low plasma concentration of methionine in our patient as well as the presence on the CSF amino acid chromatogram of a component that was tentatively identified as cystathionine, could thus be explained by an impairment of the reconversion of homocysteine into methionine, caused by a deficiency of 5-methyl-THF.…”
Section: Low Normal Plasma Methionine and Presence Of Cystathionine Imentioning
confidence: 98%
“…In vivo methionine (Met) administration will reduce formiminoglutamic acid excretion in untreated pernicious anemia and in a variety of experimental animals. In addition, Met alleviates the effects of vitamin B12 deficiency in rats and this aspect has been reviewed by SHIN et al (3). The effect of homocysteine (Homo) and Met on the DUS test has been reported by WAXMAN et al (4) and CHENG et al (5).…”
Section: Discussionmentioning
confidence: 97%
“…studied in rats and sheep. In the vitamin B12-deficient animals Met tends to over come the effect of vitamin B12 lack (3,(12)(13)(14)(15). The relevance of these observations to man however remains uncertain although a single report of RUNDLES and BREWER (16) (5) revealed this effect in vitamin B12-deficient rats.…”
Section: Discussionmentioning
confidence: 99%
“…Recent work has shown that methionine synthetase may be more important than the reductase in mediating these effects of methionine (Billings et al, 1981). The effect of the 'methyl trap', in the shape of an accumulation of N5-methyltetrahydrofolate, has been seen in cases of vitamin B 12 deficiency, and this is reversed by administration of methionine (Noronha & Silverman, 1962 Vidal & Stokstad, 1974;Davidson et al, 1975;Shin et al, 1975;Chiao & Stokstad, 1977).…”
mentioning
confidence: 99%