Effects of H4Biopterin on NOS Conformation

Importantly, increased affinity for L-arginine of brain NOS was observed not only in the presence of ITjbiopterin, but also with the oxidized product H2biopterin. Keeping in mind that the dihydro derivative is inactive as a cofactor of the enzyme, the allosteric effect that pteridines may have on the NOS protein is apparently not sufficient to support catalytic activity. Thus, binding of an appropriate pteridine derivative to NOS may convert the enzyme in an active conformation, but NO synthesis apparently requires the presence of a fully reduced biopterin. 

We have determined the kinetic parameters for the two reactions that contribute to NO inactivation in our in vitro system. Autoxidation of NO [reaction (1)] followed second- and first-order kinetics with respect to NO and oxygen, respectively, whereas autoxidation of H4biopterin [reaction (2)] was first order with respect to both H4biopterin and oxygen. 

FIGURE 2 Proposed reaction sequence of (6R)-5,6,7,8-tetrahydrobiopterin-induced oxidation of nitric oxide (NO). SOD, Superoxide dismutase. 

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