Sulfonium Ion Condensation: The Burden Borne by SAM Synthetase

Area of Science:

• Biochemistry
• Chemical Thermodynamics
• Molecular Biology

Background:

• S-Adenosylmethionine (SAM) is the primary biological methylating agent.
• The thermodynamic underpinnings of SAM's reactivity are not fully understood.
• Sulfonium ions are considered "energy-rich" due to their reactivity.

Purpose of the Study:

• To establish the thermodynamic basis for the reactivity of S-Adenosylmethionine (SAM).
• To investigate the formation and group transfer potential of S-methylmethionine (SMM).
• To elucidate the role of protonation and deprotonation in sulfonium ion energetics.

Main Methods:

• Chemical equilibrium analysis to determine the formation constant of SMM+.
• Calculation of the group transfer potential (free energy of hydrolysis) for SMM+.
• Thermodynamic analysis of thioether protonation and deprotonation.

Main Results:

• Methionine, methanol, and H+ form S-methylmethionine (SMM+) with a constant of 9.9 M-2.
• SMM+ exhibits a group transfer potential of -8.2 kcal/mol at pH 7.
• The high reactivity of sulfonium ions is linked to the acidity of S-protonated thioethers.

Conclusions:

• The thermodynamic basis for SAM's methylating ability is clarified through SMM+ analysis.
• The free energy released from deprotonation of hydrolyzed sulfonium ions contributes significantly to reactivity.
• SAM synthetase utilizes substantial energy from ATP hydrolysis to drive SAM synthesis.