Dehydrogenase aldehyde

During soya processing, volatile degradation compounds (hexanal, etc.) with a bean-like aroma defect are formed because of the enzymatic oxidation of unsaturated fatty acids. These defects can be eliminated by the enzymatic oxidation of the resultant aldehydes to carboxylic acids. Since the flavor threshold values of these acids are high, the acids generated do not interfere with the aroma improvement process. 

Of the various aldehyde dehydrogenases, the enzyme from beef liver mitochondria has a particularly high affinity for n-hexanal (Table 2.21). Hence its utilization in the production of soya milk is recommended. 

Some functional clarification of these problems has been provided by recent comparative genotyping of alcoholics and non-alcoholics. Studies in Chinese (83-85) and in Japanese (86,87), supported by meta-analysis (88), indicated significantly reduced frequencies of beta2 and gammai in alcoholics, besides the usually present aldehyde dehydrogenase deficiency (see below). It means that the high rate of ethanol conversion to the toxic and unpleasant acetaldehyde tends to reduce ethanol consumption, particularly if acetaldehyde is slowly metabolized. 

In short, the interethnic differences in the structure of ADH appear to have sufficient effects upon the fate of ethanol to be one of the determinants of alcoholism. Furthermore, one should not exclude the possibility that variation of ADH matters, for the fate of endogenous (89,90) or exogenous substrates (91,92). Ethanol is also metabolized by CYP2E1, but this enzyme is quantitatively less important than are the ADH (93). 

The clinical importance of ALDH2 deficiency for alcohol ingestion rests on the chemical reactivity and therefore toxicity of the ethanol-derived substrate acetaldehyde. It may produce facial flushing and a drop in blood pressure with tachycardia (94), i.e., effects which are perceived as an unpleasant sensation. These tend to occur after ethanol intake if the enzymatic removal of acetaldehyde is not fast enough. The unpleasantness, or even an embarassed reaction to the visual flushing, have been deterrents of excessive ethanol consumption and thereby of alcoholism. In Japan however, the deterrent effect of these sensations has been claimed to be gradually diminishing (95). 

ALDH2 occurs mostly in liver and kidney and takes the form of a tetramer which consists normally of four identical subunits. 

Goedde and Agarwal (96) list test results from 29 different populations and a total of 3248 subjects. The data can be summarized by the statements that Central Asian, East Asian, and South-East Asian populations showed deficiencies in the order of 30%. The deficiency was absent in European, Near-East, and African populations. North American Indians showed deficiency rates of 2-5%, South American Indians of 40-45%. O Dowd et al. (101) have shown that the functional enzyme deficiency in South American Indians must be due to a different mutation than the deficiency in Asians. This observation raises interesting questions regarding the biological significance of the mitochondrial aldehyde dehydrogenase. 

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Although alcohol dehydrogenases (ADH) also catalyze the oxidation of aldehydes to the corresponding acids, the rate of this reaction is significantly lower. The systems that combine ADH and aldehyde dehydrogenases (EC 1.2.1.5) (AldDH) are much more efficient. For example, HLAD catalyzes the enantioselective oxidation of a number of racemic 1,2-diols to L-a-hydroxy aldehydes which are further converted to L-a-hydroxy acids by AldDH (166). 

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... 

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. 

Chick J, Lehert P, Landron F, et al Does acamprosate improve reduction of drinking as well as aiding abstinence J Psychopharmacol 17 397-A02, 2003 Chrostek L, Jelski W, Szmitkowski M, et al Gender-related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans. J Clin Lab Anal 17 93-96, 2003... 

Lai CL, Chao YC, Chen YC, et al No sex and age influence on the expression pattern and activities of human gastric alcohol and aldehyde dehydrogenases. Alcohol Clin Exp Res 24 1625—1632, 2000... 

In some Asian populations and Native Americans, alcohol consumption results in increased adverse reactions to acetaldehyde owing to a genetic defect of mitochondrial aldehyde dehydrogenase. 

Nagy 1, G Schools, F Compermolle, P Proost, J Vanderleyden, R De Mot (1995b) Degradation of the thiocar-bamate herbicide EPTC S-ethyl dipropylcarbamoylthioate and biosafening by Rhodococcus sp. strain N186/21 involve an inducible cytochrome P-450 system and aldehyde dehydrogenase. J Bacterial 177 676-687. 

ZellnerG, A Jargon (1997) Evidence fora tungsten-stimulated aldehyde dehydrogenase activity of ZJe MZ/ovZfcrZo simplex that oxidizes aliphatic and aromatic aldehydes Arch Microbiol 168 480-485. 

Kok M, R Oldenius, MPG van der Linden, CHC Meulenberg, J Kingma, B Witholt (1989a) The Pseudomonas oleovorans alkBAC operon encodes two structurally related rubredoxins and an aldehyde dehydrogenase. J Biol Chem 264 5442-5451. 

Singer ME, WR Einnerty (1985a) Eatty aldehyde dehydrogenases in Acinetobacter sp. strain HOl-N role in hexadecane and hexadecanol metabolism. / Bacteno/ 164 1011-1016. 

Figure 17.19 A membianeless ethanol/02 enz3fme fuel cell. Alcohol dehydrogenase and aldehyde dehydrogenase catalyze a stepwise oxidation of ethanol to acetaldehyde and then to acetate, passing electrons to the anode via the mediator NAD+/NADH. At the carhon cathode, electrons are passed via the [Ru(2,2 -bipyridyl)3] and biUverdin/bilimbin couples to bilirubin oxidase, which catalyzes O2 reduction to H2O. (a) Schematic representation of the reactions occruring. (b) Power/cmrent response for the ceU operating in buffered solution at pH 7.15, containing 1 mM ethanol and 1 mM NAD. Panel (b) reprinted from Topcagic and Minteer [2006]. Copyright Elsevier, 2006.

Minteer and co-workers have also exploited the broad substrate specificity of PQQ-dependent alcohol dehydrogenase and aldehyde dehydrogenase from Gluconobacter species trapped within Nahon to oxidize either ethanol or glycerol at a fuel cell anode [Arechederra et al., 2007]. Although the alcohol dehydrogenase incorporates a series of heme electron transfer centers, it is unlikely that many enzyme molecules trapped within the mediator-free Nahon polymer are electronically engaged at the electrode. 

Disulfiram works by irreversibly blocking the enzyme aldehyde dehydrogenase, a step in the metabolism of alcohol, resulting in increased blood levels of the toxic metabolite acetaldehyde. As levels of acetaldehyde increase, the patient experiences decreased blood pressure, increased heart rate, chest pain, palpitations, dizziness, flushing, sweating, weakness, nausea and vomiting, headache, shortness of breath, blurred vision, and syncope. These effects are commonly referred to as the disulfiram-ethanol reaction. Their severity increases with the amount of alcohol that is consumed, and they may warrant emergency treatment. Disulfiram is contraindicated in patients who have cardiovascular or cerebrovascular disease, because the hypotensive effects of the disulfiram-alcohol reaction could be fatal in such patients or in combination with antihypertensive medications. Disulfiram is relatively contraindicated in patients with diabetes, hypothyroidism, epilepsy, liver disease, and kidney disease as well as impulsively suicidal patients. 

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