N-Acylethanolamines as novel alcohol dehydrogenase 3 substrates

N-Acylethanolamines (NAEs) are members of the fatty acid amide family. The NAEs have been proposed to serve as metabolic precursors to N-acylglycines (NAGs). The sequential oxidation of the NAEs by an alcohol dehydrogenase and an aldehyde dehydrogenase would yield the N-acylglycinals and/or the NAGs. Alcohol dehydrogenase 3 (ADH3) is one enzyme that might catalyze this reaction. To define a potential role for ADH3 in NAE catabolism, we synthesized a set of NAEs and evaluated these as ADH3 substrates. NAEs were oxidized by ADH3, yielding the N-acylglycinals as the product. The (V/K)app values for the NAEs included here were low relative to cinnamyl alcohol. Our data show that the NAEs can serve as alcohol dehydrogenase substrates.

Research highlights
► Alcohol dehydrogenase 3 (ADH3)-mediated oxidation of the N-acylethanolamines (NAEs).
► N-Acylglycinals are the products of NAE oxidation by ADH3.
► Structure–activity relationships for the NAE substrates.