Alcohol dehydrogenase oxidation

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

Other pathways will continue to operate but, for plasma concentrations of the order of K, an apparently linear decrease in concentration with time will be seen. Thus, for alcohol in healthy adult males, has an average value of 82 lig/ml, and an average value of 202 qg/ml/hour. About 90% of alcohol elimination is usually by the capacity-limited alcohol dehydrogenase (oxidative) pathway, the remainder being by the kidneys and other routes of excretion. The renal clearance of alcohol depends on urine flow, and is approximately equal to urine flow rate, i.e. about 1 ml/min only a trace is eliminated via the lungs. For blood-alcohol concentrations of 100, 350, 1000, and 3500 qg/ml, the elimination of alcohol will be as shown in Table 3. As the concentration rises, so the elimination rate increases (but not proportionately) to reach a value of approximately V... 

Figure 16.12. Maintaining Redox Balance. The NADH produced by the glyceraldehyde 3-phosphate dehydrogenase reaction must be reoxidized to NAD+ for the glycolytic pathway to continue. In alcoholic fermentation, alcohol dehydrogenase oxidizes NADH and generates ethanol. In lactic acid fermentation (not shovm), lactate dehydrogenase oxidizes NADH while generating lactic acid.

A single enzyme is sometimes capable of many various oxidations. In the presence of NADH (reduced nicotinamide adenine dinucleotide), cyclohexanone oxygenase from Acinetobacter NCIB9871 converts aldehydes into acids, formates of alcohols, and alcohols ketones into esters (Baeyer-Villiger reaction), phenylboronic acids into phenols sulfides into optically active sulfoxides and selenides into selenoxides [1034], Horse liver alcohol dehydrogenase oxidizes primary alcohols to acids (esters) [1035] and secondary alcohols to ketones [1036]. Horseradish peroxidase accomplishes the dehydrogenative coupling [1037] and oxidation of phenols to quinones [1038]. Mushroom polyphenol oxidase hydroxylates phenols and oxidizes them to quinones [1039]. 

AAB produce acetic acid through the oxidation of ethanol by two membrane-bound enzymes an alcohol dehydrogenase and an aldehyde dehydrogenase (Saeki et al., 1997). The alcohol dehydrogenase oxidizes ethanol to... 

In alcoholic fermentation, alcohol dehydrogenase oxidizes NADH and generates ethanol. In lactic acid fermentation (not shown), lactate dehydrogenase oxidizes NADH while generating lactic acid. 

Dehydrogenases and Oxidases An alcohol dehydrogenase oxidizes alcohols to aldehydes, which in turn are oxidized to carboxylic acids by an aldehyde dehydrogenase. Amine oxidases catalyze the oxidation of primary amines to alcohols. 

Whereas Acetobacter produces limited amounts of acetic acid through carbohydrate metabolism, much more of the acid is synthesized through the oxidation of ethanol (Eschenbruch and Dittrich, 1986). Two membrane-bound enzymes, an alcohol dehydrogenase and an aldehyde dehydrogenase, are involved in this conversion (Saeki et al., 1997). Alcohol dehydrogenase oxidizes ethanol to acetaldehyde, which is further oxidized to acetic acid hy the aldehyde dehydrogenase as follows ... 

Ethanol is the most commonly abused drug in the United States. When ingested in small amounts, ethanol may produce a feeling of euphoria in the body despite the fact that it is a depressant. In the liver, enzymes such as alcohol dehydrogenase oxidize ethanol to... 

Geotrichum candidum NAD" " alcohol dehydrogenase (Oxidized form of coenzyme) catalyzes both reactions... 

Given that transaminases are not able to aminate alcohols, one possibility for the synthesis of chiral amino alcohols is an enzyme cascade reaction carried out with whole cells [36]. Three enz3nnes cascaded in series were expressed in E. colt first the alcohol dehydrogenase oxidized tiie alcohol to the corresponding aldehyde, which is converted into the amine by the transaminase as shown in Scheme 29.15. The recycling of pyruvate and cofactor regeneration were achieved by the alanine dehydrogenase. 

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... 

The reverse reaction also occurs m living systems NADH reduces acetaldehyde to ethanol m the presence of alcohol dehydrogenase In this process NADH serves as a hydride donor and is oxidized to NAD" while acetaldehyde is reduced... 

Alcohol dehydrogenase (Section 15 11) Enzyme in the liver that catalyzes the oxidation of alcohols to aldehydes and ke tones... 

The two oxidoreductase systems most frequentiy used for preparation of chiral synthons include baker s yeast and horse hver alcohol dehydrogenase (HLAD). The use of baker s yeast has been recendy reviewed in great detail (6,163) and therefore will not be coveted here. The emphasis here is on dehydrogenase-catalyzed oxidation and reduction of alcohols, ketones, and keto acid, oxidations at unsaturated carbon, and Bayer-Vidiger oxidations. 

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). 

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... 

Step 3 of Figure 29.12 Oxidation and Decarboxylation (2K,3S)-lsocitrate, a secondary alcohol, is oxidized by NAD+ in step 3 to give the ketone oxalosuccinate, which loses C02 to givea-ketoglutarate. Catalyzed by isocitrate dehydrogenase, the decarboxylation is a typical reaction of a /3-keto acid, just like that in the acetoacetic ester synthesis (Section 22.7). The enzyme requires a divalent cation as cofactor, presumably to polarize the ketone carbonyl group. 

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... 

Formally, in redox reactions there is transfer of electrons from a donor (the reductant) to the acceptor (the oxidant), forming a redox couple or pair. Oxidations in biological systems are often reactions in which hydrogen is removed from a compound or in which oxygen is added to a compound. An example is the oxidation of ethanol to acetaldehyde and then to acetic acid where the oxidant is NAD. catalyzed by alcohol dehydrogenase and acetaldehyde dehydrogenase, respectively. 

Alcohols such as ethanol, 2-propanol, and so on, have been widely used to recycle the coenzyme for the reduction catalyzed by alcohol dehydrogenase since the enzyme catalyzes both reduction and oxidation. Usually, an excess amount of the hydrogen source is used to push the equilibrium toward formation of product alcohols. 

Reaction temperature is one of the parameters affecting the enantioselectivity of a reaction [16]. For the oxidation of an alcohol, the values of kcat/fQn were determined for the (R)- and (S)-stereodefining enantiomers E is the ratio between them. From the transition state theory, the free energy difference at the transition state between (R) and (S) enantiomers can be calculated from E (Equation 2), and AAG is in turn the function of temperature (Equation 3). The racemic temperature (% ) can be calculated as shown in (Equation 4). Using these equations, % for 2-butanol and 2-pentanol of the Thermoanaerobacter ethanolicus alcohol dehydrogenase were determined to be 26 and 77 °C, respectively. 

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. 

Alcoholism leads to fat accumulation in the liver, hyperlipidemia, and ultimately cirrhosis. The exact mechanism of action of ethanol in the long term is stiU uncertain. Ethanol consumption over a long period leads to the accumulation of fatty acids in the liver that are derived from endogenous synthesis rather than from increased mobilization from adipose tissue. There is no impairment of hepatic synthesis of protein after ethanol ingestion. Oxidation of ethanol by alcohol dehydrogenase leads to excess production of NADH. 

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