Vitamin B12 and DNA Biogenesis

Abstract

The enzyme, methylene tetrahydrofolic dehydrogenase, which mediates the reduction of one-carbon fragments from the formate to the formaldehyde level in the metabolic pathway leading to thymine methyl biogenesis, is reduced in activity in vitamin B₁₂-deficient chick livers. The addition of vitamin or coenzyme B₁₂ in vitro under aerobic conditions stimulates the deficient enzyme preparations with a K_m of 2.9 × 10^-10M. A test of the physiological significance of this stimulation has been made. Control and vitamin B₁₂-deficient chickens were injected with tracer amounts of formate-C¹⁴ and formaldehyde-C¹⁴. With either tracer the specific activity of the purines and of thymine was diminished in the bone marrow of the deficient chicks, but the percentage decrease in the specific activity of thymine was greater than the percentage decrease in the purines. No difference was observed between the 2 tracers. It is concluded that a form of vitamin B₁₂ plays a significant role in DNA synthesis, probably in the biogenesis of the thymine methyl.