Variations in the response of XXXX isozymes of @entity17417 synthetase to inhibitors of physiological relevance.

@entity3007 @entity19 @entity377 @entity17417 @entity4567 @entity860
Vertebrates have acidic and basic isozymes of @entity17417 synthetase, which participate in the first committed step of de novo @entity860 biosynthesis and/or the purine @entity377 cycle. These isozymes differ in their kinetic properties and N-leader sequences, and their regulation may vary with tissue type. Recombinant acidic and basic synthetases from @entity19 , in the presence of active site ligands, behave in analytical ultracentrifugation as dimers. Active site ligands enhance thermal stability of both isozymes. Truncated forms of both isozymes retain the kinetic parameters and the oligomerization status of the full-length proteins. @entity860 potently inhibits the acidic isozyme competitively with respect to IMP. In contrast, @entity860 weakly inhibits the basic isozyme noncompetitively with respect to all substrates. IMP inhibition of the acidic isozyme is competitive, and that of the basic isozyme noncompetitive, with respect to @entity3007 . @entity4567 potently inhibits both isozymes competitively with respect to IMP but becomes noncompetitive at saturating substrate concentrations. The above, coupled with structural information, suggests antagonistic interactions between the active sites of the basic isozyme, whereas active sites of the acidic isozyme seem functionally independent. @entity4567 and IMP together may be dynamic regulators of the basic isozyme in muscle, causing potent inhibition of the synthetase under conditions of high @entity860 deaminase activity.
