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The Anti‐Folate Effect of Methionine on Bone Marrow of Normal and Vitamin B 12 Deficient Rats
Author(s) -
Cheng F. W.,
Shane B.,
Stokstad E. L. R.
Publication year - 1975
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1975.tb00863.x
Subject(s) - methionine , vitamin b12 , homocysteine , methylation , bone marrow , methionine synthase , methyltransferase , biochemistry , cyanocobalamin , chemistry , endocrinology , vitamin , medicine , biology , amino acid , dna
S ummary . The effects of dietary vitamin B 12 and methionine deficiency, and the in vitro addition of methionine, homocysteine, or folic acid on the methylation of dUMP to dTMP were studied in rat bone marrow culture. Vitamin B 12 or methionine deficiency had no effect on the methylation reaction or on bone marrow folate levels although the vitamin B 12 content in bone marrow was reduced in vitamin B 12 deficiency. In vitro addition of vitamin B 12 or folic acid also had no effect on the methylation of dUMP. In vitro addition of methionine reduced the methylation of dUMP and increased the proportion of 5‐methyltetrahydrofolate at the expense of other folate coenzymes. The reason for this‘anti‐folate’effect of methionine, which is the opposite to that found in liver, was not clear. The presence of 5,10‐methylenetetrahydrofolate reductase and 5‐methyltetrahydrofolate‐homocysteine methyltransferase were confirmed in rat bone marrow and they were inhibited by S‐adenosylmethionine and methionine, respectively, in a similar fashion to that found with the liver enzymes. Homocysteine had no effect on the proportions of the various folate coenzymes in bone marrow but did inhibit the incorporation of deoxyuridine and deoxythymidine into DNA. It appeared that homocysteine exerted its effect at a non‐folate dependent step beyond the formation of dTMP.