Briefly explain how B12-dependent methionine synthesis acts as the rate-limiting step for intracellular accumulation of folate.

B12-dependent methionine synthesis is a crucial step in the production of S-adenosylmethionine (SAM), which is a methyl donor required for the synthesis of DNA, RNA, proteins, and other important molecules. Folate is also essential for DNA synthesis and repair, and its intracellular accumulation is dependent on the availability of SAM. Therefore, if there is a deficiency in B12-dependent methionine synthesis, there will be a decrease in SAM production, leading to a decrease in folate accumulation within the cell. This makes B12-dependent methionine synthesis the rate-limiting step for the intracellular accumulation of folate.

B12-dependent methionine synthesis is the rate-limiting step for intracellular accumulation of folate because it provides the methyl group required for the conversion of homocysteine to methionine. Folate is required for the remethylation of homocysteine to methionine, and without sufficient methionine, folate cannot be recycled and accumulates intracellularly.