The role of methionine in the intracellular accumulation and function of folates

Journal Article · Sat Jan 01 00:00:00 EST 1983 · Adv. Exp. Med. Biol.; (United States)

DOI:https://doi.org/10.1007/978-1-4757-5241-0_28· OSTI ID:5513619

Scott, J M; McKenna, B; McGing, P; Molloy, A; Dinn, J; Weir, D G

It is suggested that mammalian cells have evolved to respond to methionine deficiency since in such circumstances vital methylation reactions are put at risk, due to decreased levels of S-adenosyl-methionine. Decreased cellular homocysteine, as a result of decreased methionine, would also restrict cell division by decreased conversion of plasma 5-CH3-H/sub 4/PteGlu into intracellular polyglutamates. Cobalamin deficiency, either nutritional or due to exposure to the Co(I)cobalamin inactivating agent nitrous oxide, prevents the demethylation of 5-CH3-H/sub 4/PteGlu, which even in the presence of adequate amounts of homocysteine and methionine prevents rapidly proliferating cells from converting enough of the plasma 5-CH3-H/sub 4/ PteGlu into folylpolyglutamate forms to permit normal DNA biosynthesis and cell replication. This, together with the trapping of the cellular folate cofactors in the 5-CH3-H/sub 4/PteGlu form, results in megaloblastic changes occurring in tissues such as the marrow. The vital role of the methylation reactions was demonstrated by exposing monkeys to nitrous oxide which inactivated their methionine synthetase. The resultant ataxia and severe demyelination was prevented and diminished by methionine supplementation. When methionine synthetase was similarly inactivated in mice it was shown that while 5-CH3-H/sub 4/PteGlu enters mammalian cells, it is not converted into a polyglutamyl form and subsequently leaves the cell unmetabolised. In similar experiments in rats methionine was found to have only a small effect in restoring folylpolyglutamate biosynthesis. It was found that a decrease in the deoxythymidine salvage pathway by methionine has led others to the mistaken conclusion that methionine has an 'anti-folate' effect in bone marrow, i.e. that it decreases folate availability for thymidylate synthetase.

• Research Organization: Department of Biochemistry, Trinity College, Dublin, Ireland
• OSTI ID: 5513619
• Journal Information: Adv. Exp. Med. Biol.; (United States), Vol. 163
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
CELL DIVISION
INHIBITION
DNA
BIOSYNTHESIS
FOLIC ACID
MEMBRANE TRANSPORT
LIGASES
METHIONINE
NUTRITIONAL DEFICIENCY
NITROUS OXIDE
BIOLOGICAL EFFECTS
NUCLEOSIDES
METHYLATION
CYSTEINE
MONKEYS
VITAMIN B-12
AMINO ACIDS
ANIMALS
AROMATICS
AZAARENES
CARBOXYLIC ACIDS
CHALCOGENIDES
CHEMICAL REACTIONS
DRUGS
ENZYMES
HEMATINICS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
NITROGEN COMPOUNDS
NITROGEN OXIDES
NUCLEIC ACIDS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PRIMATES
PTERIDINES
RIBOSIDES
SYNTHESIS
THIOLS
VERTEBRATES
VITAMIN B GROUP
VITAMINS
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550200 - Biochemistry