Case 13 Inhibition of Alcohol Dehydrogenase Focus concept The inhibition of the

Question

Case 13 Inhibition of Alcohol Dehydrogenase Focus concept The inhibition of the alcohol dehydrogenase by a mnamide compound is exanned. Principles of enzyme kinetics Identification of inhibition via Lineweaver-Burk plots Background Alcohol dchydrogenase (ADiH) is the enryme that is responsibke for converting cthanol to acetakdehyde (the reaction is shown in Figure 13.1). It is the enzyme responsible for the metabolism of ethanol in the alcoholic beverages we consume. Five different isozymes of ADH have boen identifiod, and it has been showm that the enryme has a rather broad substrate specifcity and can oxidine aldchydes as well as primary and secondary akohols. For example, ADH can also oxidize methanol (wood akohol) and ethylene alcohol (antifrecze. The poisonous nature of these compounds results from the ADH-catalyzed conversion of these compounds to toxic products. For example, ADH converts methanol to formaldehyde, which is toxic to the optic nerve and ean produce blindness In high doses, formaldehyde may be fatal In this study, the authors investigated the ability of formamide compounds to inhibit alcohol dehydrogenase. Only a portion of their data is presented here. The authors were able to propose a mechanism for the inhibtion from the emensive data they collected using a wide varicty of formamide compounds. The mechanism is shown in Figure 13.2 Figure 13.1 AD-catalyzed oxidation of ethanol E-NAD E-NAD -alcohol E-NADH E-NADH-aldehyde NADH Figure 13.2 Mechanism of ADH. The inhibitor binds as an aidehyde analog.

Explanation / Answer

1) The amount of alcohol dehydrogenase (ADH) is lower in women when compared to men. ADH is needed for conversion of alcohol to aldehyde. So, in women alcohol is less efficiently broken down than men. Therefore, more alcohol enters the bloodstream of women and their blood alcohol concentration. So, women become more intoxicated than men when consuming an equal amount of alcohol.

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