A comparative study based on activity, conformation and computational analysis on the inhibition of human salivary aldehyde dehydrogenase by phthalate plasticizers: Implications in assessing the safety of packaged food items

•Phthalate plasticizers inhibit hsALDH.•The mechanism of inhibition of hsALDH by phthalates is linear mixed type.•The plasticizers induced structural changes in hsALDH.•The phthalates bind stably and efficiently near the catalytic site of hsALDH.•The study has implications in assessing the safety of packaged food items. Phthalate plasticizers are commonly used in various consumer-end products. Human salivary aldehyde dehydrogenase (hsALDH) is a detoxifying enzyme which defends us from the toxic aldehydes. Here, the effect of phthalates [Di-2-ethylhexyl phthalate (DEHP), Diethyl phthalate (DEP) and Dibutyl phthalate (DBP)] on hsALDH has been investigated. These plasticizers inhibited hsALDH, and the IC50 values were 0.48 ± 0.04, 283.20 ± 0.09 and 285.00 ± 0.14 μM for DEHP, DEP and DBP, respectively. DEHP was the most potent inhibitor among the three plasticizers. They exhibited mixed-type linear inhibition with inclination towards competitive-non-competitive inhibition. They induced both tertiary and secondary structural changes in the enzyme. Quenching of intrinsic hsALDH fluorescence in a constant manner was observed with a binding constant (Kb) of 8.91 × 106, 2.80 × 104, and 1.31 × 105 M−1, for DEHP, DEP and DBP, respectively. Computational analysis showed that these plasticizers bind stably in the proximity of hsALDH catalytic site, reciprocating via non-covalent interactions with some of the amino acids which are evolutionary conserved. Therefore, exposure to these plasticizers inhibits hsALDH which increases the risk of aldehyde induced toxicity, adversely affecting oral health. The study has implications in assessing the safety of packaged food items which utilize phthalates.