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Formic Acid

Definition

HCOOH. The toxic terminal metabolite of methanol, produced after alcohol dehydrogenase converts methanol to formaldehyde and aldehyde dehydrogenase oxidises formaldehyde to formate. Causes anion-gap metabolic acidosis and binds to cytochrome c oxidase at the optic nerve, producing blindness.

Formula
HCOOH
Source
Terminal metabolite of methanol
Pathway
Methanol to formaldehyde to formate via ADH and ALDH
Key toxic effect
Anion-gap metabolic acidosis, optic nerve injury

Common questions

Why is formic acid considered more dangerous than the methanol that produces it?+

Methanol itself is relatively low in toxicity; the danger lies in its metabolites. Once alcohol dehydrogenase and aldehyde dehydrogenase convert it stepwise to formaldehyde and then formic acid, that formic acid is what actually blocks cellular respiration and drives the acidosis and blindness seen in methanol poisoning.

Why does formic acid specifically bind cytochrome c oxidase rather than other enzymes?+

Formate has a structural and electronic affinity for the copper and heme centres of cytochrome c oxidase, complex IV of the mitochondrial electron transport chain, where it competes with oxygen for the binding site and halts ATP synthesis in oxygen-dependent tissues.

Does ethanol co-ingestion change formic acid production from methanol?+

Yes. Ethanol has a much higher affinity for alcohol dehydrogenase than methanol does, so co-ingested ethanol competitively saturates the enzyme and slows the conversion of methanol into formaldehyde and formic acid, which is the basis of using ethanol as an antidote.

Related terms

Chromotropic Acid Test
Confirmatory colour test for formaldehyde (and hence indirectly for methanol). Chromotropic acid (4,5-dihydroxy-2,7-naphthalenedisulphonic acid) plus concentrated sulphuric acid plus formaldehyde gives an...
Denatonium Benzoate
Bittering agent (Bitrex), one of the bitterest known compounds, detectable by taste at the parts-per-billion level. Added at very low concentrations to...
Denaturant
A chemical added to industrial ethanol to make it unfit for human consumption (and therefore exempt from beverage-alcohol excise). Indian Standards list...
Fomepizole
4-methylpyrazole. A competitive inhibitor of alcohol dehydrogenase used as the first-line antidote for methanol poisoning. Ethanol (oral or IV) is the older,...
Headspace GC-FID
Gas chromatography with flame-ionisation detection run on the vapour above a sealed sample. The standard forensic method for methanol and ethanol in...
Hooch
Illicit, unregulated country liquor. Indian regional names include haatch, desi tharra, and santhi. Typically distilled from molasses, jaggery, or fermented fruit, with...
Methanol
Methyl alcohol, CH3OH. Boiling point 64.7°C. Found in wood spirit, windshield-washer fluid, and as a deliberate adulterant in illicit liquor. Toxic via...

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