= Solution
\b[<finasteride> is reduced at C1, leaving a C2 <enolate> that attacks nicotinamide C4 to make the covalent C–C adduct.] In the inhibitor's unsaturated lactam, the reactive chain is $\mathrm{O{=}C3{-}C2{=}C1}$, with N at steroid position 4. Activate the C3 carbonyl by hydrogen bonding; draw the reduced cofactor's C4–H bond toward inhibitor C1, the C1=C2 pi pair toward C2–C3, and the C3=O pi pair toward <oxygen>. This gives <NADP+> next to the C2-centered resonance form of the inhibitor <enolate>.
Instead of completing reduction by protonating C2, move the C2 <lone pair> toward the electrophilic C4 of the oxidized nicotinamide ring. Shift the pyridinium pi system toward its positively charged N, and reform the inhibitor carbonyl if using the oxygen-centered <enolate> representation. The result is the \b[C2(inhibitor)–C4(nicotinamide) bond] and a neutral dihydronicotinamide ring. Numbering the two molecules separately prevents confusing cofactor C4 with the inhibitor's N4. The lactam N–H remains present and can help position the inhibitor through hydrogen bonding; it does not form a covalent bond to the protein.
This is <mechanism-based inhibition>: enzyme chemistry generates the species that traps its own oxidized cofactor. Isolation of a cofactor–inhibitor adduct after protein denaturation, rather than persistent attachment to a denatured protein, distinguishes it from covalent modification of an amino acid side chain. The original mechanistic study combined radiolabel recovery, purification and spectroscopy to establish the adduct; its slow breakdown also cautions against treating “irreversible” as an absolute statement for every timescale.<Mechanism-Based Inhibition of Human Steroid 5α-Reductase by Finasteride: Enzyme-Catalyzed Formation of NADP–Dihydrofinasteride, a Potent Bisubstrate Analog Inhibitor by Herbert G. Bull and others>[1996, pp. 2361–2363, adduct isolation, structural analysis and Fig. 7]{ref}
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