The inhibition of the alcohol dehydrogenase by a formamide compound is examined. Alcohol dehydrogenase (ADH) is the enzyme responsible for converting ethanol to acetaldehyde.
H3C + CH2 - OH + NAD+ rightarrow ADH H3C - CH = O + NADH, H+
Ethanol --> Acetaldehyde
It is the enzyme responsible for the metabolism of ethanol in the beverages we consume. 5 different isoenzymes of ADH have been identified, and it has been shown that the enzyme has rather a broad substrate specificity and can oxidize aldehydes as well as primary and secondary alcohols. For example, ADH converts methanol to formaldehyde, 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 ability of formaldehyde compounds to inhibit alcohol dehydrogenase. Only a portion of their data is presented here. The authors were able to propose a mechanism for the inhibition from the extensive data they collected using a wide variety of formamide compounds.
rate - limitingstepE + NAD+ arrow E - NAD+ + alcohol arrow E - NAD+ -
alcohol arrow E - NADH - aldehyde arrow -aldehyde ENADH + I arrow E - NADH -I arrow-I
E - NADH arrow -NADH E(rate - limitingstep)
A treatment for methanol poisoning is to have the victim drink large amounts of ethanol. Why might this be an effective treatment?