Fig. 8.
The methylfolate trap hypothesis. Reaction (a) is held to be irreversible under physiological conditions so that reaction (b) is the only metabolic escape for methylfolate. When reaction (b) is inhibited by either a deficiency of vitamin B12 or by cyanocobalamin [c-lactam], folate should be trapped as methylfolate. S-adenosyl methionine has a negative effect on reaction (a) so that inhibition of reaction (b) should effectively increase the flow of 5,10-methylene tetrahydrofolate towards methylfolate. CH3-THF, 5-methyl tetrahydrofolate; 5,10-CH2-THF, 5,10-methylene tetrahydrofolate; THF, tetrahdrofolate. Reaction (a), methylene tetrahydrofolate reductase. Reaction (b), methionine synthase.