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Author Notes:

Ruma Banerjee: rbanerje@umich.edu.

The authors declare no competing financial interest.


Research Funding:

This work was supported in part by grants from the National Institutes of Health (DK45776 to R.B., 5 F32 GM113405 to G.C.C. and DK054514 to K.W.); and the National Science Foundation (CHE 1710339 to T.C.B.).


  • Science & Technology
  • Physical Sciences
  • Chemistry, Multidisciplinary
  • Chemistry

Sacrificial Cobalt-Carbon Bond Homolysis in Coenzyme B-12 as a Cofactor Conservation Strategy

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Journal Title:

Journal of the American Chemical Society


Volume 140, Number 41


, Pages 13205-13208

Type of Work:

Article | Post-print: After Peer Review


A sophisticated intracellular trafficking pathway in humans is used to tailor vitamin B12 into its active cofactor forms, and to deliver it to two known B12-dependent enzymes. Herein, we report an unexpected strategy for cellular retention of B12, an essential and reactive cofactor. If methylmalonyl-CoA mutase is unavailable to accept the coenzyme B12 product of adenosyltransferase, the latter catalyzes homolytic scission of the cobalt-carbon bond in an unconventional reversal of the nucleophilic displacement reaction that was used to make it. The resulting homolysis product binds more tightly to adenosyltransferase than does coenzyme B12, facilitating cofactor retention. We have trapped, and characterized spectroscopically, an intermediate in which the cobalt-carbon bond is weakened prior to being broken. The physiological relevance of this sacrificial catalytic activity for cofactor retention is supported by the significantly lower coenzyme B12 concentration in patients with dysfunctional methylmalonyl-CoA mutase but normal adenosyltransferase activity.

Copyright information:

© 2018 American Chemical Society.

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