Alcohol dehydrogenase acts via zero-order kinetics. Zero-order kinetics is characterized by the elimination of a constant quantity of the drug per time unit. Contrast this with first-order kinetics in which the proportion of the drug that is excreted is constant, but the actual quantity that is eliminated depends on the drug concentration.
Metabolism of ethanol begins in the cytoplasm of cells, where it is converted into acetaldehyde by alcohol dehydrogenase.
Ethanol is turned into acetaldehyde by alcohol dehydrogenase, which operates via zero-order kinetics. This enzyme is located in the cytosol. CYP2E1 enzyme of Microsomal Ethanol-Oxidizing System (MEOS) also plays a role in the metabolism of ethanol into acetaldehyde, and its activation in chronic alcohol consumption results in depletion of NADPH and formation of free radicals, which can cause peroxidation of membranes and damage hepatocytes. Catalase enzyme also plays a minor role in alcohol oxidation and converts toxic hydrogen peroxide into water.
Alcohol dehydrogenase consumes NAD and forms NADH. This results in an increased NADH/NAD ratio, which decreases gluconeogenesis, increases ketogenesis and increases lipogenesis.
Acetaldehyde is produced by the metabolism of ethanol by alcohol dehydrogenase. Increased levels of acetaldehyde are responsible for the hangover symptoms.
Acetaldehyde is converted into acetate by acetaldehyde dehydrogenase. This enzyme is located in the mitochondria.
Alcohol dehydrogenase and acetaldehyde dehydrogenase both consume NAD and produce NADH. Thus, the metabolism of ethanol results in an increased NADH/NAD ratio, which decreases conversion of oxaloacetate into malate. This, in turn, results in decreased gluconeogenesis, and increased risk of fasting hypoglycemia. Increased NADH/NAD ratio also increases conversion of pyruvate into lactate, which can result in lactic acidosis.
Metabolism of acetaldehyde by acetaldehyde dehydrogenase results in the formation of acetate in the mitochondria.
Acetate thiokinase is an enzyme that converts acetate into acetyl-CoA.
Acetate is converted to acetyl-CoA by the action of acetate thiokinase. Increased NADH/NAD ratio results in the diversion of acetyl-CoA into the synthesis of ketones instead of the TCA cycle. Increased NADH also results in the diversion of acetyl-CoA into fatty acid synthesis, which can result in hepatosteatosis (fatty liver).
Fomepizole is a medication that is used for the treatment of methanol and ethylene glycol poisonings.
Fomepizole blocks alcohol dehydrogenase and prevents the conversion of ethanol into acetaldehyde; by blocking this enzyme it also prevents the metabolism of toxic byproducts of methanol and ethylene glycol.
Disulfiram blocks acetaldehyde dehydrogenase and prevents the conversion of acetaldehyde into acetate. Accumulation of acetaldehyde leads to symptoms of a hangover; this discourages patients from drinking alcohol.
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