Acetaldehyde metabolism

The oxidation of acetaldehyde to acetic acid has been studied with NAD-linked ALDH purified from human, rat and Syrian hamster liver (Klyosov et al., 1996). The mitochondrial enzymes from these species have very similar kinetic properties, whereas human cytosolic ALDHl has a value of about 180 pM, compared with 15 pM and 12 pM for rats and hamsters, respectively. Apparently, in human liver, only mitochondrial ALDH oxidizes acetaldehyde at physiological concentrations, whereas both mitochondrial and cytosolic ALDHs of rodents can participate in acetaldehyde metabolism. The rodent cytosolic ALDHs are at least 10 times more sensitive that the human enzyme to inhibition by disulfiram. 

Osborne, J.P., Mira de Orduna, R., Pilone, G.l., Liu, S.Q. (2000). Acetaldehyde metabolism by wine lactic acid bacteria. FEMS Microbiol. Lett., 191, 51-55. 

H. Riveros-Rosas, A. Julian-Sanchez, and E. Pina. 1997. Enzymology of ethanol and acetaldehyde metabolism in mammals Arc/z. Med. Res. 28 453-471. (PubMed)... 

Pronko PS, Satanovskaya VI, Gorenstein BI, Kuzmich AB, Pyzhik TN. 2002. Effect of pyruvate, threonine and phospho-ethanolamine on blood endogenous acetaldehyde metabolism in rats with toxic liver injury. Voprosy Meditsinskoi Khimii 48 278-85... 

KlyosovAA, Rashkovetsky LG, Tahir MK, KeungW-M (1996) Possible role of liver cytosolic and mitochondrial aldehyde dehydrogenases in acetaldehyde metabolism. Biochemistry 35 4445-4456... 

Uncertain. One suggested mechanism is a disulfiram-like inhibition of acetaldehyde metabolism by trichloroethylene (see Alcohol + Disulfiram , p.61). Another suggested mechanism is inhibition of trichloroethylene metabolism in the presence of alcohol, resulting in increased plasma levels and possibly an accumulation of trichloroethylene in the CNS. ... 

Both RALDHl and RALDH2 inefficiently catalyze acetaldehyde metabolism in vitro. Nevertheless, one wonders whether the acetaldehyde produced during chronic alcohol intake competes with retinal metabolism, perhaps contributing to fetal alcohol syndrome. This simple postulate, however, has complex caveats. Not the least of which includes the imprudence of ascribing a specific mechanism to a highly reactive non-specific agent. 

Many biological processes involve oxidation of alcohols to carbonyl compounds or the reverse process reduction of carbonyl compounds to alcohols Ethanol for example is metabolized m the liver to acetaldehyde Such processes are catalyzed by enzymes the enzyme that catalyzes the oxidation of ethanol is called alcohol dehydrogenase... 

Anesthesia. Materials that have unquestionable anesthetic properties are chloral hydrate [302-17-0] paraldehyde, dimethoxymethane [109-87-5] and acetaldehyde diethyl acetal. In iadustrial exposures, however, any action as an anesthesia is overshadowed by effects as a primary irritant, which prevent voluntary inhalation of any significant quantities. The small quantities which can be tolerated by inhalation are usually metabolized so rapidly that no anesthetic symptoms occur. 

Yeast (qv) metabolize maltose and glucose sugars via the Embden-Meyerhof pathway to pymvate, and via acetaldehyde to ethanol. AH distiUers yeast strains can be expected to produce 6% (v/v) ethanol from a mash containing 11% (w/v) starch. Ethanol concentration up to 18% can be tolerated by some yeasts. Secondary products (congeners) arise during fermentation and are retained in the distiUation of whiskey. These include aldehydes, esters, and higher alcohols (fusel oHs). NaturaHy occurring lactic acid bacteria may simultaneously ferment within the mash and contribute to the whiskey flavor profile. 

Ethanol metabolism occurs mainly in the liver and proceeds by oxidation in two steps, first to acetaldehyde (CHjCHO) and then to acetic add (CH3CO2H)- When continuously present in the body, ethanol and acetaldehyde are toxic, leading to the devastating physical and metabolic deterioration... 

Alcohol dehydrogenase is a cytoplasmic enzyme mainly found in the liver, but also in the stomach. The enzyme accomplishes the first step of ethanol metabolism, oxidation to acetaldehyde, which is further metabolized by aldehyde dehydrogenase. Quantitatively, the oxidation of ethanol is more or less independent of the blood concentration and constant with time, i.e. it follows zero-order kinetics (pharmacokinetics). On average, a 70-kg person oxidizes about 10 ml of ethanol per hour. 

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... 

C2H5OH, ethanol is formed by bacteria in the gastrointestinal tract in low amounts. Most of the ethanol of bacterial source is metabolized during the first liver passage yielding acetaldehyde and subsequently acetic acid. 

Ethanol is oxidized by alcohol dehydrogenase (in the presence of nicotinamide adenine dinucleotide [NAD]) or the microsomal ethanol oxidizing system (MEOS) (in the presence of reduced nicotinamide adenine dinucleotide phosphate [NADPH]). Acetaldehyde, the first product in ethanol oxidation, is metabolized to acetic acid by aldehyde dehydrogenase in the presence of NAD. Acetic acid is broken down through the citric acid cycle to carbon dioxide (CO2) and water (H2O). Impairment of the metabolism of acetaldehyde to acetic acid is the major mechanism of action of disulfiram for the treatment of alcoholism. 

Aune H, Renck H, Bessen A Metabolism of diethyl ether to acetaldehyde in man (letter). Lancet 2 97, 1978... 

The metabolism of NMOR in the rat is outlined in Figure 4. o-Hydroxylation yields the unstable intermediates and the latter hydrolyzes to (2-hydroxyethoxy)acetaldehyde [7] which has been identified as a liver microsomal metabolite by isolation of the corresponding 2,4-dinitrophenylhydrazone (59). (2-Hydroxy-ethoxy)acetaldehyde, which exists predominantly as the cyclic hemiacetal was not detected in the urine of rats gavaged with 125 mg/kg NMOR. However, (2-hydroxyethoxy)acetic acid was a major urinary metabolite (16% of the dose). These transformations are analogous to those observed with NPYR and NNN. 

Aerobic living features metabolize sugars and fatty acids to carbon dioxide. Accordingly, there are some kinds of decarboxylation reactions. TPP-mediated decarboxylation of pyruvic acid to acetaldehyde is one of the most important steps of the metabolism of sugar compounds (Fig. 1). When the intermediate reacts with lipoic acid instead of a proton, pyruvic acid is converted to acetylcoenzyme A, which is introduced to TCA cycle (Fig. 2). 

Alcohol abuse is a major clinical problem in many countries and has been the subject of investigation for many years by those interested in determining the molecular basis of ethanol-induced liver dam e (see Lieber, 1990). These intensive and extended efforts have revealed much about the metabolism of ethanol in the liver and about the toxicity of its primary oxidative product, acetaldehyde. They have not, however, folly elucidated the molecular mechanisms that lead to the typical features of alcoholic liver injury steatosis, necrosis and eventually cirrhosis. 

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