Adenosyl radical: reagent and catalyst in enzyme reactions

Area of Science:

• Biochemistry
• Enzymology
• Evolutionary Biology

Background:

• Adenosine is a fundamental biological molecule, a component of essential cofactors like ATP, FADH, NAD(P)H, and RNA.
• This review focuses on adenosine's role in its highly reactive organic radical form.

Purpose of the Study:

• To provide an overview of adenosine's function as a radical cofactor.
• To discuss enzymes utilizing adenosylcobalamin (AdoCbl) and S-adenosylmethionine (AdoMet) radical species.
• To explore the evolutionary origins and mechanistic insights of these radical enzymes.

Main Methods:

• Review of existing literature on radical adenosine enzymes.
• Analysis of reaction mechanisms, particularly hydrogen atom migrations.
• Comparison of AdoCbl-dependent and radical-AdoMet enzyme families.

Main Results:

• AdoCbl-dependent enzymes catalyze specific rearrangement reactions involving 1,2-hydrogen atom migrations.
• Radical-AdoMet enzymes catalyze a broad spectrum of challenging chemical transformations.
• Many radical enzymes are oxygen-sensitive, suggesting ancient anaerobic origins.

Conclusions:

• Adenosine's radical cofactor role likely emerged early in evolution, predating oxygenic photosynthesis.
• Studying these enzymes provides valuable mechanistic understanding of radical intermediate generation and control.
• Emerging evidence suggests potential activity of radical-AdoMet enzymes in aerobic organisms, including humans.