Case 13 Inhibition of Alcohol Dehydrogenase Focus concept The inhibition of the alcohol dehydrogemase by a formamide compound is examined Prerequisites Principles of enzyme kinetics Idenification of inhibition via Lineweaver-Bark plots Background Alcohol dchydrogenase (ADiH) is the enayme 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 been identifiod, and i has been shown that the cnuayme has a rather broad substrate specificity and can oxidizne akdchydes as well as primary and secondary akcohols. For example, ADH ean also oxidize methanol (wood akobol) and ethylene alcohol (antifreeze). The poisonous nature of these compounds results from the ADH-catalyzed conversion of these compounds to toxic products. For example, ADH converts methanol to formakdehyde, which is toxic to the optic nerve and can produce blindness In high doses, formaldehyde may be fatal In this study, the authors investigated the abiliny 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 NAH H, O ADH Ethand NAD Figure 13.1:AD-catalyzed oxidation of ethanol. alcohol NAD E-NADE-NAD -alcohol NADHl E-NADH- Figure 13.2: Mechanism of ADH1. The inhibitor binds as an aldehyde analog. Solution When methanol is consumed it is converted to methanal (formaldehyde)using alcohol dehydrogenase enzyme, which is toxic to optic nerve and can cause blindness. This situation is handled with consuming large amount of ethanol or injecting alcohol solution intravenous. The large quantity of alcohols swamps the alcohol dehydrogenase enzyme( which is responsible for the conversion of methanol to formaldehyde) to act upon alcohol. This swamping provides time for kidneys to excrete out methanol from the blood to urine. In this way methanol poisoning can be handled. .

1. Case 13 Inhibition of Alcohol Dehydrogenase Focus concept The inhibition of the alcohol
dehydrogemase by a formamide compound is examined Prerequisites Principles of enzyme
kinetics Idenification of inhibition via Lineweaver-Bark plots Background Alcohol
dchydrogenase (ADiH) is the enayme 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 been identifiod,
and i has been shown that the cnuayme has a rather broad substrate specificity and can oxidizne
akdchydes as well as primary and secondary akcohols. For example, ADH ean also oxidize
methanol (wood akobol) and ethylene alcohol (antifreeze). The poisonous nature of these
compounds results from the ADH-catalyzed conversion of these compounds to toxic products.
For example, ADH converts methanol to formakdehyde, which is toxic to the optic nerve and
can produce blindness In high doses, formaldehyde may be fatal In this study, the authors
investigated the abiliny 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 NAH H, O ADH Ethand NAD Figure 13.1:AD-
catalyzed oxidation of ethanol. alcohol NAD E-NADE-NAD -alcohol NADHl E-NADH- Figure
13.2: Mechanism of ADH1. The inhibitor binds as an aldehyde analog.
Solution
When methanol is consumed it is converted to methanal (formaldehyde)using alcohol
dehydrogenase enzyme, which is toxic to optic nerve and can cause blindness. This situation is
handled with consuming large amount of ethanol or injecting alcohol solution intravenous. The
large quantity of alcohols swamps the alcohol dehydrogenase enzyme( which is responsible for
the conversion of methanol to formaldehyde) to act upon alcohol. This swamping provides time
for kidneys to excrete out methanol from the blood to urine.
In this way methanol poisoning can be handled.