Navigating the B12 Road: Assimilation, Delivery, and Disorders of Cobalamin

The reactivity of the cobalt-carbon bond in cobalamins is the key to their chemical versatility, supporting both methyl transfer and isomerization reactions. During evolution of higher eukaryotes that utilize vitamin B-12, the high reactivity of the cofactor coupled with its low abundance pressured development of an efficient system for uptake, assimilation, and delivery of the cofactor to client B-12-dependent enzymes. Although most proteins suspected to be involved in B-12 trafficking were discovered by 2009, the recent identification of a new protein reveals that the quest for elucidating the intracellular B-12 highway is still far from complete. Herein, we review the biochemistry of cobalamin trafficking.