Liver formaldehyde dehydrogenase

Goodman JI, Trephly TR. 1971. A comparison of rat and human liver formaldehyde dehydrogenase. Biochim Biophys Acta 252 489-505. 

Liver alcohol dehydrogenase (ADH) is relatively nonspecific and will oxidize ethanol or other alcohols, including methanol. Methanol oxidation yields formaldehyde, which is quite toxic, causing, among other things, blindness. Mistaking it for the cheap... 

MARTINEZ, M.C., ACHKOR, H., PERSSON, B., FERNANDEZ, M.R., SHAFQAT, J., FARRES, J., JORNVALL, H., PARES, X., Arabidopsis formaldehyde dehydrogenase. Molecular properties of plant class III alcohol dehydrogenase provide further insights into the origins, structure and function of plant class P and liver class I alcohol dehydrogenases, Eur. J. Biochem., 1996,241, 849-857. 

N-1 ormy [piperidine (4.15) is an uncompetitive inhibitor of liver alcohol dehydrogenase (Figure 4.18).14 Liver alcohol dehydrogenase is often associated with the oxidation of ethanol in the bloodstream, but it also oxidizes methanol to formaldehyde, which is a toxic metabolite. Safe, effective inhibitors of liver alcohol dehydrogenase represent a potential treatment for individuals who have ingested methanol. 

Formic acid can be readily absorbed from the digestive tract and the respiratory system. Systemic absorption produces acidosis, neuropathy, and visual and mental disturbances. Acidosis can also be produced when formic acid is produced by liver aldehyde dehydrogenase from formaldehyde. Formaldehyde in turn can also be produced metabolically by alcohol dehydrogenase from methanol. Formic acid is oxidized to carbon dioxide by the folate-dependent pathway. Some formic acid is excreted unchanged in the urine. 

Pocker Y, Li H. 1990. Kinetics and mechanism of methanol and formaldehyde interconversion and formaldehyde oxidation catalyzed by liver alcohol dehydrogenase. Adv Exp Med Biol 284 315-325. 

Heck H d A, Casanova-Schmitz M, Dodd PB, Schachter EN, Witek TJ, Tosim T (1985) Formaldehyde (CH2O) concentrations in the blood of humans and Fischer-344 rats exposed to CH2O under controlled conditions. Am Ind Hyg Assoc J 46 1-3 Uotila L, Koivusalo M (1974) Formaldehyde dehydrogenase from human liver. Purification, properties, and evidence for the formation of glutathione thiol esters by the enzyme. J Biol Chem 249 7653-7663... 

A method [116] was developed for determining formate as benzimidazole after reaction with o-phenylenediamine at 130 °C for 2 h in 1M perchloric acid. The benzimidazole was extracted from the reaction mixture with ethyl acetate/ethanol (9 1, v/v). The HPLC system was a Cjg column, isocratic elution with a mixture of phosphate buffer (pH 2.1) and acetonitrile, and detection at 267 nm. This procedure was employed to determine the formate concentration in human urine and rat liver and urine, and to measure the activity of formaldehyde dehydrogenase [116]. 

TA medical therapy based on competition at the active site is used to treat patients who have ingested methanol, a solvent found in gas-line antifreeze. The liver enzyme alcohol dehydrogenase converts methanol to formaldehyde, which is damaging to many tissues. Blindness is a common result of methanol ingestion, because... 

Formaldehyde can also be produced in the body Drinking wood alcohol (methanol) causes blindness, respiratory failure, convulsions, and death. The liver enzyme alcohol dehydrogenase, whose function it is to detoxify alcohols, catalyzes the conversion of methanol to formaldehyde (methanal). The formalde-... 

Ethanol is metabolized in a two step process (see figure below), according to zero order kinetics. As the drug passes through the liver, it is first dehydrated by alcohol dehydrogenase, forming acetaldehyde (which dissociates into methanol and formaldehyde, should the next metabolic step be inhibited). Acetaldehyde is then metabolized by aldehyde dehydrogenase into acetate, which may then enter the citric acid cycle. 

The high toxicity, by injection, of methanol is due to reaction (11.42), in which it is oxidised to formaldehyde. This reaction is catalysed by the enzyme alcohol dehydrogenase which is present in the liver. 

Although methanol itself is not particularly harmful, accidental or intentional ingestion of methanol can cause headache, nausea, blindness, seizures, and even death. In the liver, methanol is metabolized by the enzyme alcohol dehydrogenase (ADH) to yield formaldehyde ... 

FH4 can also react chemically nth formaldehyde as shown in experiments by Blakley (43) and Kisliuk (44) and the product so formed is able to react enzymically with glycine to form serine. In biological systems, however, the donor of the single-carbon unit to FH4 at the HCHO level of oxidation may be serine via the serine hydroxymethylase reaction (4S). Recently an enzyme termed hydroxymethyl-FH4 dehydrogenase that catalyzes the interconversion of 10-hydrox3rmethyl-FH4 and 10-formyl-FH4 or their respective ring anhydrides by triphosphopyridine nucleotide has been purified from beef liver by Hatefi et al. (46). This important enzyme links the two derivatives of FH4 that function metabolically at either the formyl or formaldehyde level of oxidation. 

The human toxicology of methanol has been studied [6,71,72]. The skin absorption rate has been reported to be 0.19 m cm2/min [73]. Methanol vapor uptake by the lungs is effective, usually 7080% (74). In the liver, methanol goes through oxidation metabolism catalyzed by alcohol dehydrogenase (an enzyme), producing toxic formaldehyde and formic acid. The accumulation of formic acid leads to acidosis, dama g the nervous system, particularly the optic nerves, and the retina. In the copresence of ethanol, ethanol is selectively metabolized by alcohol dehydrogenase over methanol this delays methanol intoxication and allows detoxication by the natural elimination of methanol via respiration and urination. The methanol elimination half-life is about 23 h [6]. Because of the slow elimination, methanol can be re rded as a cumulative poison [68]. Chronic oq)osure may result in sufficient methanol accumulation in the body, and illness. 

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