4. Liver alcohol dehydrogenase (LADH) catalyzes a reversible, pH-dependent oxidation of an alcohol to an aldehyde according to the following reaction: LADH RCH2OH NAD* RCHO NADH H* + + + where NAD* and NADH are, respectively, the oxidized and reduced forms of the cofactor nicotin-amide adenine dinucleotide. While the reaction is actually a two-substrate reaction, it proceeds like a one- substrate reaction through a so-called compulsory-ordered ternary complex mechanism. It has been shown through kinetic studies that, in the case of primary alcohols, the enzyme binds first the cofactor forming a binary enzyme-NAD* complex that then binds the second substrate, the alcohol, to form a ternary enzyme-NAD*-substrate complex in which the oxidation of the alcohol proceeds with reduction of the cofactor. While the enzyme catalyzes oxidation of various steroids as well as ingested ethanol, it also catalyzes the oxidation of methanol CH3OH, forming the extremely toxic product formaldehyde HCHO. Inges-tion of methanol, depending on the amount, results in blindness or death. Blindness results through damage to the retinol dehydrogenase in our retina. The remedy for methanol ingestion is to ingest or be given intravenous ethanol. (Actually the patient becomes quite inebriated under these conditions.) Under these conditions, ethanol acts as a competitive inhibitor of methanol oxidation, displacing it from LADH. This action provides sufficient time for the methanol to be harmlessly excreted by the kidneys. If an individual has ingested 100 mL of methanol (a lethal dose), how much 100 proof whiskey (50% ethanol by volume) must he imbibe to reduce the activity of his LADH toward methanol to 5% of its original value? The adult human body contains -40 L of aqueous fluids throughout which ingested alcohols are rapidly and uniformly mixed. The densities of ethanol and methanol are both 0.79 g/cm3. Assume the KM values of LADH for ethanol and methanol to be 1.0 x 10-3 M and 1.0 x 10-2 M, respectively, and that Ki = KM for ethanol. Will the patient survive?

4. Liver alcohol dehydrogenase (LADH) catalyzes a reversible, pH-dependent oxidation of an alcohol to an aldehyde according to the following reaction: LADH RCH2OH NAD* RCHO NADH H* + + + where NAD* and NADH are, respectively, the oxidized and reduced forms of the cofactor nicotin-amide adenine dinucleotide. While the reaction is actually a two-substrate reaction, it proceeds like a one- substrate reaction through a so-called compulsory-ordered ternary complex mechanism. It has been shown through kinetic studies that, in the case of primary alcohols, the enzyme binds first the cofactor forming a binary enzyme-NAD* complex that then binds the second substrate, the alcohol, to form a ternary enzyme-NAD*-substrate complex in which the oxidation of the alcohol proceeds with reduction of the cofactor. While the enzyme catalyzes oxidation of various steroids as well as ingested ethanol, it also catalyzes the oxidation of methanol CH3OH, forming the extremely toxic product formaldehyde HCHO. Inges-tion of methanol, depending on the amount, results in blindness or death. Blindness results through damage to the retinol dehydrogenase in our retina. The remedy for methanol ingestion is to ingest or be given intravenous ethanol. (Actually the patient becomes quite inebriated under these conditions.) Under these conditions, ethanol acts as a competitive inhibitor of methanol oxidation, displacing it from LADH. This action provides sufficient time for the methanol to be harmlessly excreted by the kidneys. If an individual has ingested 100 mL of methanol (a lethal dose), how much 100 proof whiskey (50% ethanol by volume) must he imbibe to reduce the activity of his LADH toward methanol to 5% of its original value? The adult human body contains -40 L of aqueous fluids throughout which ingested alcohols are rapidly and uniformly mixed. The densities of ethanol and methanol are both 0.79 g/cm3. Assume the KM values of LADH for ethanol and methanol to be 1.0 x 10-3 M and 1.0 x 10-2 M, respectively, and that Ki = KM for ethanol. Will the patient survive?

Biochemistry

6th Edition

ISBN:9781305577206

Author:Reginald H. Garrett, Charles M. Grisham

Publisher:Reginald H. Garrett, Charles M. Grisham

Chapter18: Glycolysis

Section: Chapter Questions

Problem 23P: Examine the ActiveModel for alcohol dehydrogenase and describe the structure and function of the...

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