Isotope selective activation: a new insight into the catalytic activity of urease

Abstract

Urease, a metalloenzyme, requires carbon dioxide (CO₂) for its activation. But, whether this activation is isotope-specific to ¹²CO₂ or ¹³CO₂, is not yet known and even the potential role of CO₂ in the enzymatic activity of urease is poorly understood. Here, we provide direct experimental evidence that the catalytic activity of urease exhibits a unique isotope-specific response where the ¹²CO₂ isotope is strongly preferred over the ¹³CO₂ isotope during its catalytic activation. Moreover, this isotope-selective activation depends on different isotopic fractionations (¹²C:¹³C) of the reaction-environment as well as the substrate urea (¹³C-urea and ¹²C-urea), where the ¹²CO₂ isotope in the reaction medium essentially facilitates the hydrolysis of ¹³C-enriched urea. This deepens our understanding of the isotope-specific urease activation and its potential role in hydrolytic reaction. Our findings thus may offer novel opportunities for a better fundamental understanding of isotope-specificity in chemical reactions involving metalloenzymes.