Metabolism of methanol

ADH also has clinical significance in the metabolism of methanol and ethylene glycol, two drugs with toxic metabolites. Methanol is oxidized by ADH to formaldehyde, which damages the retina and can cause blindness. Ethylene glycol is metabohzed by ADH to oxalic acid, which has renal tox-... 

Management of methanol and ethylene glycol poisoning is similar. Symptomatic support of respiration and circulation is augmented by correction of metabolic acidosis with intravenous bicarbonate infusion, and control of seizures with diazepam. Ethanol inhibits the metabolism of methanol and ethylene glycol to the toxic metabolites, and can give time for further treatment. The goal is to maintain blood ethanol concentrations between 100 and 150 mg per decilitre, sufficient to saturate alcohol... 

Ethanol Higher affinity for alcohol dehydrogenase used to reduce metabolism of methanol and ethylene glycol to toxic products ... 

The administration of ethanol to a patient suffering from methanol intoxication will competitively inhibit the metabolism of methanol to formaldehyde and... 

Figure 7.85 The metabolism of methanol. Abbreviations. ADH, alcohol dehydrogenase MEOS, microsomal ethanol-oxidizing system ALDH, aldehyde dehydrogenase THF, tetrahydrofolate.

Inhibiting methanol metabolism. Ethanol, which occupies the dehydrogenase enzymes in preference to methanol, competitively prevents metabolism of methanol to its toxic products. A single oral dose of ethanol 1 ml/kg (as a 50% solution or as the equivalent in gin or whisky) is followed by 0.25 ml/kg/h orally or i.v., aiming to maintain the blood ethanol at about... 

In industry, exposure to formic acid can occur through the oral, dermal, and inhalation routes. Formic acid can also be produced in the mouth and stomach from ingested formaldehyde. Formic acid can also be produced in the liver and other organs from the metabolism of methanol and formaldehyde. Stings by bees, wasps, and ants may result in the subcutaneous injection of formic acid. 

Side note Methanol Poisoning. An interesting and imponant example competitive substrate inhibition is the enzyme alcohol dehydrogenase (AC in the presence of ethanol and methanol. If a person ingests methanol, Al will convert it to formaldehyde and then formate, which causes blindne Consequently, the treatment involves intravenously injecting ethanol (wh is metabolized at a slower rate than methanol at a controlled rate to tie ADH to slow the metabolism of methanol-to-formaldehyde-to-formate so l the kidneys have time to filter out the methanol which is then excreted in urine. With this treatment, blindness is avoided. For more on the met nol/ethanol competitive inhibition, see Problem P7 2Sc. 

In all poisoning situations, it is important to establish adequate respiration. Bicarbonate may be needed to counteract metabolic acidosis. In patients with suspected methanol intoxication, ethanol (10% solution) is often given intravenously before laboratory diagnosis is confirmed to block the formation of toxic products of ADH-catalyzed metabolism of methanol. Blood levels of methanol in excess of 50 mg/dL are an absolute indication for hemodialysis. Activated charcoal does not bind alcohols. The answer is (B). 

A. Methanol is slowly metabolized by alcohol dehydrogenase to formaldehyde and subsequently by aldehyde dehydrogenase to formic acid (formate). Systemic acidosis is caused by both formate and lactate, while blindness is caused primarily by formate. Both ethanol and methanol compete for the enzyme alcohol dehydrogenase, and block the metabolism of methanol to its toxic metabolites. 

We learned at the beginning of the ch ter that alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) catalyze the metabolism of methanol. In analogous reactions, ADH and ALDH catalyze the metabolism of ethanol, the alcohol in alcoholic beverages. 

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