Dehydrogenases, alcohol and aldehyde

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... 

Structural and Kinetic Features of Alcohol and Aldehyde Dehydrogenase I 421... 

Smith M. Genetics of human alcohol and aldehyde dehydrogenases. Adv Human Genet 1986 15 249-290. 

Beside the MMFO mediated (phase I) reactions there are a few other major reactions that are worthy of note. The two major ones involve ester hydrolysis and alcohol and aldehyde dehydrogenases. All mammalian species have an extensive ability to hydrolyze the ester bond. The products of the reactions then can go on to be further metabolized. In the pharmaceutical industry, this property has been utilized to synthesize prodrugs that is, chemicals that have desirable pharmaceutical properties (generally increased water solubility) that are not converted to their active moiety until hydrolyzed in the body. 

Methyl alcohol is only used to denature ethyl alcohol in 5 percent concentration. It is metabolised to formaldehyde and formic acid by alcohol and aldehyde dehydrogenases. Its absorption and distribution are similar to ethyl alcohol. 

Oxidation Cytochrome P450s Prostaglandin synthetase Flavin-containing monooxygenases Alcohol and aldehyde dehydrogenases... 

Many other significant polymorphisms in xenobiotic metabolizing enzymes have been described, including those for several CYP genes, alcohol and aldehyde dehydrogenases, epoxide hydrolase, and paraoxonase. One interesting polymorphism affecting... 

C-H Wong, JR Matos. Enantioselective oxidation of 1,2-diols to L-a-hydroxy acids using co-immobilized alcohol and aldehyde dehydrogenases as catalysts. J Org Chem 50 1992-1994, 1985. 

Bosron WF, Li TK. Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatology 1986 6 502-510. 

Chao YC, Liou SR, Chung YY, Tang HS, Hsu CT, Li TK, Yin SJ. Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients. Hepatology 1994 19 360-366. 

Several studies have been aimed at elucidating the relationship between the activity of particular flor yeast enzymes during velum production, both in lab-scale and under winery conditions. For example, studies on the activity of alcohol and aldehyde dehydrogenase have... 

Mauricio, J. C., Moreno, J. J., and Ortega, J. M. (1997). In vitro specific activities of alcohol and aldehyde dehydrogenases from two flor yeasts during controlled wine aging.. Agric. Food Chem. 45,1967-1971. 

Carbonyl reductases and alcohol and aldehyde dehydrogenases are cytosolic enzymes being involved in the oxidation of alcohols and aldehydes and in the reduction of aldehydes and ketones (Lang and Kalgutkar 2003). 

Since liver is the most important organ for metabolism investigations the procedures described here focus on liver cytosol exemplarily. Liver cytosol fraction contains soluble Phase I and Phase II enzymes which play an important role in drug metabolism (Brandon 2003). These are alcohol and aldehyde dehydrogenases, epoxide hydrolases, sulfotransferases, glutathione S transferase, N-acetyl transferases, and methyl transferases. Therefore, in cytosolic preparations these biotransformation steps can be studied. Cytosolic fractions are commercially available (BDGentest, Invitro Technologies, Xenotech and others) or easy to prepare, alternatively. 

Conditions for cytosolic incubations depend on the aim of the assay e.g. to cover specific enzymatic activity present in the cytosol. For this purpose it is essential to fortify the incubation medium with the specific cofactor for the reaction-if needed (Ekins 1999). (J> -Nicotinamide adenine dinucleotide (NAD) is needed for alcohol and aldehyde dehydrogenases, flavin adenine dinucleotide (FAD) for polyamine oxidase, P-nicotinamide adenine dinucleotide phosphate (NADPH) for Dihydropyrimidine dehydrogenase. Phase II reactions depend on PAPS (sulfotransferases,... 

Panes J, Soler X, Pares A, et al. (1989) Influence of liver disease on hepatic alcohol and aldehyde dehydrogenases. Gastroenterology 97 708-714. 

Methanol is widely available as a solvent and in paints and antifreezes, and may be consumed as a cheap substitute for ethanol. As little as 10 ml may cause permanent blindness and 30 ml may kill, through its toxic metabolites. Methanol, like ethanol, is metabolised by zero-order processes that involve the hepatic alcohol and aldehyde dehydrogenases, but whereas ethanol forms acetaldehyde and acetic acid which are partly responsible for the unpleasant effects of hangover, methanol forms formaldehyde and formic acid. Blindness may occur because aldehyde dehydrogenase present in the retina (for the interconversion of retinol and retinene) allows the local formation of formaldehyde. Acidosis is due to the formic acid, which itself enhances pH-dependent hepatic lactate production, so that lactic acidosis is added. 

A disulfiram-like effect (see p. 186) occurs with alcohol because metronidazole inhibits alcohol and aldehyde dehydrogenase patients should be warned appropriately. 

Boston, WJ ., Li, T.K. Genetic determinations of alcohol and aldehyd dehydrogenases and alcohol metabolism. Semin. Liver Dis. 1981 1 179-188... 

Other mono-oxygenases are not cytochrome P450 dependent, such as flavoproteins located in the endoplasmic reticulum that are involved in the oxidation of tertiary amines to N-oxides and of various sulfur compounds. Yet other oxidative enzymes, including alcohol and aldehyde dehydrogenases and monoamine oxidases, are located in the mitochondria or cytosol. 

As mentioned previously, both alcohol and aldehyde dehydrogenases can function as reductases in the presence of NAD. In addition, there are a number of other carbonyl reductases that are NADP" "-dependent. Aldehyde reductases and carbonyl reductases are localized in the cytosol of cells, have a... 

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

Higuchi.S. etal. (1995) Alcohol and aldehyde dehydrogenase polymorphisma and... 

Of the Phase I reactions, oxidative biotransformations are by far the most common. These reactions are carried out by several oxidative enzyme systems, the most predominant of which is the CYP superfamily of enzymes. Additional oxidative enzymes include FMO, xanthine oxidase, aldehyde oxidase, alcohol and aldehyde dehydrogenases monoamine oxidases, and various peroxidases. Determining the enzyme(s) employed to biotransform any particular substrate will depend on the substrates chemical and physical characteristics as well as functional substituents. This chapter does not describe in detail the mechanism of these various enzymes however, it does illustrate the product(s) (i.e., metabolites) produced by each reaction. 

Ghanayem BI, Burka LT, Matthews HB. 1987b. Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity role of alcohol and aldehyde dehydrogenases. J Pharmacol Exp Ther 242(1) 222-231. 

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