The puzzle of how a vitamin B₁₂ derivative is activated in living organisms could soon be solved, according to a US scientist.

Coenzymes are non-protein components of enzymes that are necessary for enzyme function yet organisms cannot make them from scratch. Kenneth Brown from Ohio University studied coenzyme B₁₂, the coenzyme form of vitamin B₁₂, and found that its activation by enzymes could be aided by compression of a key metal­-nitrogen bond. 

Coenzyme B₁₂ has the unique feature of a cobalt ion in its structure, which is coordinated by a nucleotide attached to a side chain. Brown was examining whether manipulating the bond that joins the coenzyme to its nucleotide ligand plays a role in the activation of the coenzyme. 

Around a dozen enzymes are known to require coenzyme B₁₂ for activity. For each one, the first step of the catalytic cycle is breaking a carbon-cobalt bond. Compression of the cobalt-nucleotide bond on the opposite face of the metal could activate the coenzyme by stabilizing the organic radical ion produced in this first step, said Brown.

Recent advances in the study of coenzyme B₁₂, mainly using NMR and x-ray crystallography methods, have led to the proposal of new mechanisms and modeling of coenzyme B₁₂  dependent enzyme active sites, said Brown. These advances show that coenzyme B₁₂ dependent enzymes fall into several classes, and it is likely that there will be different mechanisms for each, he continued. 

'It is reasonable to expect that a full understanding of how at least one such enzyme activates coenzyme B₁₂ can be achieved in the next five years,' said Brown. 

Katherine Vickers