Liver alcohol dehydrogenase methanol

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... 

The enzyme chemistry of cyclopropylmethanols has been studied both as inhibitors and mechanistic probes [4, 47]. Thus, a series of alkylcyclopropyl-methanol derivatives have been proved as being inhibitors of horse liver alcohol dehydrogenase. There are two sites in the cyclopropylmethanol inhibitors able of reacting with nucleophiles ... 

Horse liver alcohol dehydrogenase is able to oxidise primary alcohols—except methanol—and to reduce a large number of aldehydes. Aqueous solution or organic solvents can be used [62]. As there are no new developments concerning this enzyme, the reader is referred to the review of Schreier [1]. 

Uncompetitive inilibitors of liver alcohol dehydrogenase (Chapter 15) could be used to treat cases of poisoning by methanol or ethylene glycol.81 83 The aim is to prevent rapid oxidation to the toxic acids HCOOH and HOCH2COOH, which lower blood pH, while the alcohols are excreted. Uncompetitive inhibitors have an advantage over competitive inhibitors as therapeutic agents in that the inhibition is not overcome when the substrate concentration is saturating.84... 

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. 

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. 

The tris(2-mercapto-l-mesitylimidazolyl)borate ligand, TmMs, reacts with Zn(C104)2-6H20 yielding [Zn(TmMs)(HOMe)]+, a stable monomeric tetrahedral zinc-methanol complex which shows analogies with the alcohol intermediate in the catalytic cycle of the mechanism of action of liver alcohol dehydrogenase.57... 

The mechanism of liver alcohol dehydrogenase (LADH) has been extensively studied. For a recent overview the reader is referred to Ref [93]. Reaction field effects on the transition structure of model hydride transfer systems have been calculated at ab initio 4-3IG basis set level [93, 94]. The active site of enzymes are usually assumed to be designed to receive molecules in the transition state for the reaction they catalyze. This special sort of surrounding medium effects has been computationally documented recently [95]. From the reaction geodesic passing through the transition state for hybride transfer in the pyridium cation/methanolate model system, only the TS-structure could be fitted into the LADH active site. The normal mode analysis carried out on the TS showed an excellent agreement with isotopic substitution experiments [95]. Reaction field calculations on this model systems have also been performed. For an overview of biomolecular interactions the reader is referred to Ref [96]. 

The rate constant for the incorporation of lead into the cryptand (2,1,1) in methanol is unusually high and reflects the high selectivity of this ligand for over the alkaline-earth-metal ions. The kinetics of metal-loporphyrin formation have been reviewed with particular reference to the metal-ion-assisted mechanism, and the kinetics and mechanism of the recombination of Co ", Ni ", and Zn " with the metal-depleted catalytic site of horse liver alcohol dehydrogenase have been reported. ... 

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... 

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. 

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 ... 

A variety of alcohols, in addition to methanol and ethanol, are oxidized in mammalian species among these are butanol, fluoroethanol, cyclohexanol, and 2-phenylethanoL These oxidations are catalysed by alcohol dehydrogenase which is localized in the soluble fraction of mammalian liver, lung, and kidney. 

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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