Vitamin B12 and drug development

The consumption of vitamin B12 (B12), also known as cobalamin (Cbl), is essential for humans. B12 is produced naturally by select bacteria (and likely certain archea) (Doxey et al. 2015) and organisms must acquire the vitamin through their diet (about 2.5 pg per day for humans) (Martens et al. 2002; Nielsen et al. 2012). There are two primary biologically active forms of B12: methylcobalamin and adenosylcobalamin. Methionine synthase uses methylcobalamin to produce the amino acid methionine from homocysteine, and methylmalonyl-CoA mutase uses adenosylcobalamin as a cofactor to produce succinyl CoA (Nielsen et al., 2012; Kräutler 2005). Mammals have developed a complex dietary uptake pathway for B12 involving a series of transport proteins and specific receptors across various tissues and organs (vide infra) (Nielsen et al., 2012; Gherasim et al. 2013). It is the understanding and exploitation of this uptake pathway that offers considerable scope for drug development.