Aldehyde dehydrogenase inhibition

ME is metabolized to 2-mercaptoacetate by alcohol and aldehyde dehydrogenase. Inhibition of alcohol dehydrogenase in experimental animals, blocking the... 

The mechanism of this interaction is not understood. It has been proposed that tacrolimus may act on the same biochemical pathway as alcohol potentiating a capsaicin-mediated release of neuropeptides, which increase vasodilatory effects. Alternatively, cutaneous aldehyde dehydrogenase inhibition in areas where tacrolimus has been applied may increase cutaneous aldehyde levels that, through prostaglandins as mediators, could lead to vasodilation following alcohol consumption. - ... 

Ethanol is almost entirely metabolized in the liver. The first step, oxidation by alcohol dehydrogenase, yields acetaldehyde, a reactive and toxic compound. Essentially all of the acetaldehyde is converted to acetate by the liver enzyme aldehyde dehydrogenase. Aldehyde dehydrogenase is inhibited by the drag disulfiram. Given alone, disulfiram is a nontoxic substance. However, ethanol consumption in the presence of... 

Mitchell, D.Y. and D.R. Petersen. 1988. Inhibition of rat liver aldehyde dehydrogenases by acrolein. Drug Metabol. Dispos. 16 37 42. 

N, O-Diacylated or O-alkylated N-hydroxysulfonamides release nitroxyl (HNO) upon hydrolysis or metabolic dealkylation, as determined by gas chromatographic identification of nitrous oxide in the reaction headspace [27-29, 38]. Scheme 7.5 depicts the decomposition of a representative compound (7) to a C-acyl nitroso species that hydrolyzes to yield HNO. Either hydrolysis or metabolism removes the O-acyl or O-alkyl group to give an N-hydroxy species that rapidly decomposes to give a sulfinic acid and an acyl nitroso species. This C-acyl nitroso species (8) hydrolyzes to the carboxylic acid and HNO (Scheme 7.5). These compounds demonstrate the ability to relax smooth muscle preparations in vitro and also inhibit aldehyde dehydrogenase, similar to other HNO donors [27, 29]. 

Segal and Blair (S13) have shown that aldehydes reduce NAD to NADH2 in the presence of aldehyde dehydrogenase progesterone, menthol, and menthone inhibit this enzyme and this may account for the stimulatory action shown by these substances on galactose metabolism in vitro. 

Vallari RC, Pietruszko R. Human aldehyde dehydrogenase mechanism of inhibition of disulfi-ram. Science 1982 216(4546) 637-639. 

The effect is mainly due to the inhibition of NAD+-dependent aldehyde dehydrogenase (ALDH) which causes an accumulation of acetaldehyde in the body after ethanol ingestion [17]. The compound responsible for the physiological activity of C. atramentarius is coprine 16, a AT -(l-hydroxycyclopropyl)-L-glutamic acid amide which has been isolated and synthesized, [16a,b]. Thus, when fed... 

Most of the human experience with disulfiram has come from its use as an avoidance therapy for alcoholism. Metabolites of disulfiram inhibit aldehyde dehydrogenase, resulting in elevated levels of acetaldehyde after ethanol ingestion. Side effects include flushing of the face, tachycardia, severe headache, apprehension, hyperpnea, hypotension, dizziness, nausea, vomiting, and fainting. Severe reactions may include convulsions, myocardial infarction, and marked respiratory depression. ... 

Kenel MF, Kulkarni AP. 1985a. Ethanol potentiation of carbon tetrachloride hepatotoxicity possible role for the in wVo inhibition of aldehyde dehydrogenase. Gen Pharmacol 16 355-360. 

Kenel MF, Kulkarni AP. 1985b. Inhibition of hepatic aldehyde dehydrogenase by carbon tetrachloride an in vitro study. Int J Biochem 17 605-610. 

It exerts its action by inhibiting aldehyde dehydrogenase enz5une. Disulfiram thus increases the concentration of acetaldehyde in body when ethanol is ingested by an individual pretreated with disulfiram. The symptoms and signs produced... 

Metabolism of ethanol by alcohol dehydrogenase and the microsomal ethanol-oxidizing system (MEOS). Alcohol dehydrogenase and aldehyde dehydrogenase are inhibited by fomepizole and disulfiram, respectively. NAD +, nicotinamide adenine dinucleotide NADPH, nicotinamide adenine dinucleotide phosphate. 

Methanol is converted to the toxic metabolites formaldehyde and formate by alcohol dehydrogenase and aldehyde dehydrogenase. By inhibiting alcohol dehydrogenase, ethanol and fomepizole reduce the formation of toxic metabolites. 

Disulfiram Inhibits aldehyde dehydrogenase, causes aldehyde accumulation during ethanol ingestion Deterrent to relapse in individuals with alcoholism Toxicity Little effect on its own but severe and potentially dangerous flushing, headache, nausea, vomiting, and hypotension when combined with ethanol... 

Inhibits hepatic microsomal drug-metabolizing enzymes. Inhibits aldehyde dehydrogenase. 

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