Ethanol works as a competitive substrate for alcohol dehydrogenase, inhibiting the metabolism of xenobiotics like methanol and ethylene glycol that use this enzyme.
The dose of ethanol necessary to achieve competitive inhibition depends on the relative concentrations of the toxic alcohols and their affinity for the enzyme. An affinity constant, Km, is used to express the degree of affinity: the lower the Km value, the stronger the affinity. The following equates mmol or mg for alcohols: 1 mmol ethanol equals 46 mg, 1 mmol methanol equals 32 mg, and 1 mmol ethylene glycol equals 64 mg. A millimolar concentration means mmoles/L. A summary of in vitro experiments using human liver cells demonstrated a Km of 30 mM for ethylene glycol, 7 mM for methanol, and 0.45 mM for ethanol.29,42,43 This means that the molar affinity of ethanol for alcohol dehydrogenase is 67 times that of ethylene glycol and 15.5 times that of methanol. Studies in methanol-poisoned monkeys revealed that when ethanol was administered at a molar ethanol-to-methanol ratio (E:M) of 1:4, the metabolism of methanol was reduced by 70%; at a 1:1 E:M ratio, metabolism was reduced by greater than 90%.32 In these experiments, the dose of methanol was kept constant at about 1 g/kg (31 mmol/kg), whereas the dose of ethanol was varied. Although the serum methanol concentration was not measured, a calculation using this dose and a volume of distribution (Vd) of 0.6 L/kg would predict a serum concentration of about 166 mg/dL. Even in molar ratios as high as 1:8, methanol did not inhibit ethanol metabolism. When ethylene glycol and methanol are administered together in a 0.5:1 molar ratio, ethylene glycol did not inhibit methanol metabolism.32 When compared with methanol smaller amounts of ethanol are required to block the metabolism of ethylene glycol, as the affinity of ethylene glycol for alcohol dehydrogenase is less than that of methanol.22,29,42,43,45,51 Most authors1,22,51 recommend either a serum ethanol concentration of 100 mg/dL, or at least a 1:4 molar ratio of ethanol to methanol or ethylene glycol, whichever is greater. Using this ratio, 100 mg/dL (∼ 22 mmol/L) of ethanol protects against 88 mmol/L (286 mg/dL) of methanol or 88 mmol/L (546 mg/dL) of ethylene glycol. Inhibiting the metabolism of methanol and ethylene glycol impedes the formation of toxic metabolites and prevents the development of metabolic acidosis.13,16,21,51 After this toxic metabolic pathway is blocked with ethanol, renal, pulmonary, and extracorporeal routes of toxic alcohol removal become the sole mechanisms for elimination.