Vitamin B₁₂ in the spotlight again.

Area of Science:

• Biochemistry
• Enzymology
• Bioinorganic Chemistry

Background:

• Cobalamin's diverse reactivity stems from its ability to coordinate various upper axial ligands.
• Traditionally, adenosylcobalamin and methylcobalamin were linked to radical rearrangements and methyl cation transfers, respectively.
• Recent research expands our understanding of cobalamin's roles and mechanisms.

Purpose of the Study:

• To explore the diverse reactivity of cobalamin based on its axial ligands.
• To highlight newly discovered functions of adenosylcobalamin and methylcobalamin.
• To review emerging information on ligand-independent cobalamin enzymes and cobalamin-dependent radical enzymes.

Main Methods:

• Literature review of recent studies on cobalamin-dependent enzymes.
• Analysis of established and novel cobalamin reactivities.
• Investigation of mechanistic details in cobalamin-mediated reactions.

Main Results:

• Adenosylcobalamin functions as a light sensor, and methylcobalamin may transfer methyl anions.
• A third class of cobalamin enzymes, lacking upper ligands, performs reductive dehalogenations and epoxide reductions.
• Mechanistic insights are emerging for cobalamin-dependent S-adenosylmethionine radical enzymes.

Conclusions:

• Cobalamin exhibits a broader range of functions and mechanisms than previously understood.
• New roles in light sensing, anion transfer, and ligand-independent catalysis are established.
• Further research is elucidating the enigmatic roles of cobalamin in radical enzyme superfamilies.