Alcohol dehydrogenase pyrazole inhibition

Primary alcohols are oxidized to aldehydes, n-butanol being the substrate oxidized at the highest rate. Although secondary alcohols are oxidized to ketones, the rate is less than for primary alcohols, and tertiary alcohols are not readily oxidized. Alcohol dehydrogenase is inhibited by a number of heterocyclic compounds such as pyrazole, imidazole, and their derivatives. 

The initial rates (v in juM/min) of liver alcohol dehydrogenase-catalyzed ethanal reduction are measured in the presence of pyrazole as an inhibitor at the constant concentration of NADH (0.02 M) and the constant concentration of ethanal (2.0 mM), respectively. Propose respective inhibition types and estimate their inhibition constants. 

Total body clearance occurs by metabolic clearance and by renal excretion. The excretion of propylene glycol is species dependent. Humans clear 45% of propylene glycol via kidney, and in dogs, up to 88%. In rats and rabbits, very little of the parent compound is excreted by the kidney until saturation of metabolism occurs. Inhibition of alcohol dehydrogenase by pyrazole increases urinary excretion of propylene glycol to 75% in rats. 

Human alcohol dehydrogenase isoenzymes have been divided into three classes. Class I isoenzymes contain a, p, yl, and y2 subunit isoenzymes, are cationic at neutral pH, and are strongly inhibited by substituted pyrazole inhibitors. Class II isoenzymes contain the 7i isoenzyme subunit, are cationic at neutral pH, and are relatively insensitive to pyrazole inhibition. Class III isoenzymes contain the X subunit, are anionic at neutral pH and are insensitive to pyrazole inhibitors. 

Methyl pyrazole has been developed as a long-acting and less toxic alternative to ethanol in the treatment of ethylene glycol poisoning. Shown is a Lineweaver-Burk plot of the inhibition of alcohol dehydrogenase by various concentrations of 4-methyl pyrazole. What type of inhibidon appears to be exhibited by this molecule ... 

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