Intermediates in Enzymatic Reactions

The two oxidation states of (17) that are relevant in biopterin-dependent redox reactions are the four-electron and two-electron reduced forms, tetrahydrobiopterin (19) and p-quinonoid dihydrobiopterin (20), respectively. The oxidation state between these two, i.e. a radical, may also be relevant though it has not been detected as an intermediate in enzymatic reactions. Structurally, pteridines and flavins are rather similar and hence show similar chemical behavior in many respects. As a redox coenzyme, (19) is not encountered nearly as frequently as nicotinamides or flavins. It is, however, the cofactor of three very... 

The inversion of configuration during an SN2 reaction has led to certain criteria for the detection of intermediates in enzymatic reactions. For example, suppose that an enzyme catalyzes the nucleophilic reaction 8.22. Then a direct attack of Y on the alkyl halide will lead to inversion. But if the substrate first reacts with a nucleophilic group on the enzyme to give an intermediate that then reacts with Y (equation 8.24),... 

We saw in Chapter 7 that much effort has been put into the detection of chemical intermediates in enzymatic reactions. It has been found, though, that these do not accumulate in the reactions of many of the most common hydrolytic enzymes with their natural substrates under physiological conditions (Table 12.5). 

In the past three decades, evidence for enzyme-based protein radicals as the catalytic driving force or the key transient intermediate in enzymatic reactions has strengthened (11). Spectroscopic data from EPR suggest that these highly reactive species can be stored with remarkable stability inside an enzyme either as a transient intermediate or as a paramagnetic center and catalyze a wide range of biological reactions in electron transfer and oxidation/reduction. 

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