Mechanism of thermal decomposition of carbamoyl phosphate and its stabilization by aspartate and ornithine transcarbamoylases.

ABSTRACT: Carbamoyl phosphate (CP) has a half-life for thermal decomposition of <2 s at 100 degrees C, yet this critical metabolic intermediate is found even in organisms that grow at 95-100 degrees C. We show here that the binding of CP to the enzymes aspartate and ornithine transcarbamoylase reduces the rate of thermal decomposition of CP by a factor of >5,000. Both of these transcarbamoylases use an ordered-binding mechanism in which CP binds first, allowing the formation of an enzyme.CP complex. To understand how the enzyme.CP complex is able to stabilize CP we investigated the mechanism of the thermal decomposition of CP in aqueous solution in the absence and presence of enzyme. By quantum mechanics/molecular mechanics calculations we show that the critical step in the thermal decomposition of

SUBMITTER: Wang Q 

PROVIDER: S-EPMC2579353 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature