Question

How and why can b12 defiecency lead to homocysteine?

Answer 1

In humans, only two enzymatic reactions are known to be dependent on vitamin B12. In the first reaction, methylmalonic acid is converted to succinyl-CoA using vitamin B12 as a cofactor . Vitamin B12 deficiency, therefore, can lead to increased levels of serum methylmalonic acid. In the second reaction, homocysteine is converted to methionine by using vitamin B12 and folic acid as cofactors. In this reaction, a deficiency of vitamin B12 or folic acid may lead to increased homocysteine levels.

An understanding of the vitamin B12 absorption cycle helps illuminate the potential causes of deficiency. The acidic environment of the stomach facilitates the breakdown of vitamin B12 that is bound to food. Intrinsic factor, which is released by parietal cells in the stomach, binds to vitamin B12 in the duodenum. This vitamin B12–intrinsic factor complex subsequently aids in the absorption of vitamin B12 in the terminal ileum.

In addition to this method of absorption, evidence supports the existence of an alternate system that is independent of intrinsic factor or even an intact terminal ileum. Approximately 1 percent of a large oral dose of vitamin B12 is absorbed by this second mechanism.This pathway is important in relation to oral replacement. Once absorbed, vitamin B12 binds to transcobalamin II and is transported throughout the body. The interruption of one or any combination of these steps places a person at risk of developing deficiency.

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