A potentially interesting paper.
I do not feel that I understand anything beyond what the highlights say.
I can see that fuller understanding is desirable. Though I am finding it difficult see any advantages to analogs in this era of readily available "real" B12. However, if these analogs could be absorbed even by those who have impaired absorption of B12, they might have some role.
As so often, the full paper is behind a paywall.
Naturally occurring cobalamin (B12) analogs can function as cofactors for human methylmalonyl-CoA mutase
Olga M.Sokolovskaya, Tanja Plessl, Henry Bailey, Sabrina Mackinnon, Matthias R.Baumgartnerc, Wyatt W.Yued, D. Sean Froesec, Michiko E.Taga
doi.org/10.1016/j.biochi.20...
Highlights
• Human MMUT can use naturally occurring vitamin B12 analogs (cobamides) as cofactors.
• Cobamide affinity for MMUT and binding kinetics vary based on cobamide structure.
• Cobamides that bind MMUT support catalysis, with differences in apparent KM.
• Some cobamides also support the activity of disease-associated MMUT variants.
• Unexplored implications of cobamide diversity in human health are considered.
Abstract
Cobalamin, commonly known as vitamin B12, is an essential micronutrient for humans because of its role as an enzyme cofactor. Cobalamin is one of over a dozen structurally related compounds – cobamides – that are found in certain foods and are produced by microorganisms in the human gut. Very little is known about how different cobamides affect B12-dependent metabolism in human cells. Here, we test in vitro how diverse cobamide cofactors affect the function of methylmalonyl-CoA mutase (MMUT), one of two cobalamin-dependent enzymes in humans. We find that, although cobalamin is the most effective cofactor for MMUT, multiple cobamides support MMUT function with differences in binding affinity (Kd), binding kinetics (kon), and concentration dependence during catalysis (KM, app). Additionally, we find that six disease-associated MMUT variants that cause cobalamin-responsive impairments in enzymatic activity also respond to other cobamides, with the extent of catalytic rescue dependent on the identity of the cobamide. Our studies challenge the exclusive focus on cobalamin in the context of human physiology, indicate that diverse cobamides can support the function of a human enzyme, and suggest future directions that will improve our understanding of the roles of different cobamides in human biology.