Figure 58.

Use of ¹⁸O labeling studies in defining the mechanism of P450 19A1.^{177,220,222,223} Steps 1 and 2 are generally agreed to involve the P450 FeO³⁺ entity and hydrogen atom abstraction/oxygen rebound.²²⁴ Two possibilities are shown for Step 3 in the presence of ¹⁸O₂. In Step 3a, the Fe^III–O₂⁻ entity participates in a nucleophilic attack on the 19-aldehyde. In Step 3b, the FeO³⁺ form of the P450 19A1 abstracts the 1β-hydrogen atom of the gem-diol. Electron transfer yields the carbocation, which collapses to yield the estrogen product. In Step 3a, the HCO₂H must contain label (¹⁸O) but not in Step 3b. “*O” denotes ¹⁸O. The step 3(b) pathway is supported by recent evidence.¹⁷⁷