Abstract
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 mu M 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-noncompetitive 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 (K-b) of 8.91 x 10(6), 2.80 x 10(4), and 1.31 x 10(5) 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