Inhibition of human cytochrome P450 2E1 and 2A6 by aldehydes: structure and activity relationships.

•Human P450 2E1 and 2A6 active sites were probed using a series of small aldehydes.•Both enzymes preferred α,β-unsaturated aldehydes to corresponding saturated forms.•Branching in the aldehyde reduced binding to both isoforms.•The 2E1 active site appeared to expand in response to α,β-unsaturation.•The aldehydes were oxidized by 2E1, but not 2A6.