Formate (Formic Acid)
Definition
The terminal toxic metabolite of methanol oxidation (HCOO-, pKa 3.7). Formate inhibits cytochrome c oxidase (mitochondrial complex IV), causing optic nerve and basal ganglia necrosis; it also drives severe anion-gap metabolic acidosis as it accumulates.
- Chemical form
- HCOO-, conjugate base of formic acid
- pKa
- 3.7
- Mechanism
- Inhibits cytochrome c oxidase (complex IV)
- Target tissues
- Optic nerve and basal ganglia
- Clinical sign
- Anion-gap metabolic acidosis
Common questions
Why does formate selectively damage the optic nerve rather than causing generalised tissue injury?+
The optic nerve and retina have a very high mitochondrial density and oxygen demand, making them especially vulnerable when cytochrome c oxidase is blocked and ATP production falls, which is why visual symptoms often appear before other organ effects in methanol poisoning.
How is formate level used clinically or post-mortem to assess methanol exposure severity?+
A rising formate concentration correlates with severity of acidosis and visual toxicity better than the parent methanol level alone, because methanol itself is not directly toxic. Serum formate or blood gas anion-gap trends are used alongside methanol levels to guide treatment and, post-mortem, to support cause-of-death interpretation.
What treatment slows formate accumulation in methanol poisoning?+
Fomepizole or ethanol competitively blocks alcohol dehydrogenase, the enzyme that converts methanol into toxic metabolites, slowing further formate production while the patient is supported and, in severe cases, given haemodialysis to remove existing methanol and formate.
Related terms
- Alcohol Dehydrogenase (ADH)
- The hepatic enzyme (isoforms ADH1A, ADH1B, ADH1C) that catalyses the first oxidation step of both ethanol (to acetaldehyde) and methanol (to formaldehyde)...
- Anion-Gap Metabolic Acidosis
- The metabolic acid-base disorder produced by accumulating formate in methanol poisoning. The anion gap (Na+ - [Cl- + HCO3-], normal 8-12 mEq/L)...
- Congener Fingerprinting
- The use of the full volatile congener profile (fusel alcohols, acetaldehyde, ethyl acetate, pyridine, MIBK) in illicit liquor samples to establish batch...
- Fomepizole (4-Methylpyrazole)
- A specific competitive inhibitor of alcohol dehydrogenase (Ki approximately 0.1 µM), used as the preferred antidote for methanol poisoning in high-resource settings....
- FSSAI Methanol Limit
- Under India's Food Safety and Standards (Alcoholic Beverages) Regulations 2018, the maximum methanol content permitted in legally produced and sold spirits is...
- Haemodialysis in Methanol Poisoning
- The most efficient treatment for removing both methanol and formate from circulation and correcting severe metabolic acidosis. The EXTRIP workgroup (US) and...
- Latency Period
- The 12-24 hour window between methanol ingestion and onset of severe symptoms (visual disturbance, metabolic acidosis), during which the patient may appear...
- Pyridine
- An aromatic nitrogen heterocycle used as a secondary denaturant in Indian denatured spirit formulations (at 1-2% v/v). Its presence in a headspace...
- Vitreous Humour
- The gel-filled interior of the eye, anatomically isolated from hepatic and gastric post-mortem redistribution sources. In forensic toxicology of hooch deaths, vitreous...