Promoter ethanol dehydrogenase

Thus, the role of zinc in the dehydrogenation reaction is to promote deprotonation of the alcohol, thereby enhancing hydride transfer from the zinc alkoxide intermediate. Conversely, in the reverse hydrogenation reaction, its role is to enhance the electrophilicity of the carbonyl carbon atom. Alcohol dehydrogenases are exquisitely stereo specific and by binding their substrate via a three-point attachment site (Figure 12.7), they can distinguish between the two-methylene protons of the prochiral ethanol molecule. 

Ethanol has been shown to block the metabolism of 2-butoxyethanol to 2-butoxyacetic acid through competitive inhibition of alcohol dehydrogenase (Romer et al. 1985). Administration of ethanol after 2-butoxyethanol exposure can be used to control the production of toxic metabolites and to promote conjugation of the parent compound to nontoxic products of elimination such as the glucuronide and sulfate conjugates. This approach has been recommended for clinical therapy for 2-butoxyethanol poisoning (Buckley et al. 1993). 

Butandiol was used as a smart cosubstrate to promote NAD(P)H reductase-dependent reactions. 7-Butyrolactone, the product of two successive essentially irreversible enzyme-catalyzed oxidations, is thermodynamically stable and chemically inert that drives the reaction strongly in the direction of substrate reduction. The authors examined the reduction of NAD(P)+ by 1,4-butanediol with 12 commercially available reductases, 8 of which successfully accepted the diol substrate. In the reduction of cinnamaldehyde with horse liver dehydrogenase, both the initial rate and maximum conversion were higher with 1,4-butan-diol than with alternative sacrificial reductants such as iso-propanol or ethanol (Scheme 6.33) [48]. 

---