A Detoxication Route for Acetaldehyde: Metabolism of Diacetyl, Acetoin, and 2,3-Butanediol in Liver Homogenate and Perfused Liver of Rats

Otsuka, Masato; Mine, Tomoharu; Ohuchi, Kentarou; Ohmori, Shinji

doi:10.1093/oxfordjournals.jbchem.a021230

Cited by 63 publications

(39 citation statements)

References 16 publications

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“…This supports the general function of the enzyme in the uronate cycle. As previously suggested for diacetyl reductase (21), DCXR also acts as a detoxification enzyme toward reactive dicarbonyl compounds, which are formed in the tissue or ingested as components of foods and beverages (32). In addition, the co-distribution of DCXR and carboxymethyllysine in the renal tubules led us to speculate that DCXR may interact with the dicarbonyl precursors of AGEs.…”

Section: Discussionmentioning

confidence: 51%

Molecular Characterization of Mammalian Dicarbonyl/l-Xylulose Reductase and Its Localization in Kidney

Nakagawa¹,

Ishikura²,

Asami³

et al. 2002

Journal of Biological Chemistry

146

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In this report, we first cloned a cDNA for a protein that is highly expressed in mouse kidney and then isolated its counterparts in human, rat hamster, and guinea pig by polymerase chain reaction-based cloning. The cDNAs of the five species encoded polypeptides of 244 amino acids, which shared more than 85% identity with each other and showed high identity with a human sperm 34-kDa protein, P34H, as well as a murine lungspecific carbonyl reductase of the short-chain dehydrogenase/reductase superfamily. In particular, the human protein is identical to P34H, except for one amino acid substitution. The purified recombinant proteins of the five species were about 100-kDa homotetramers with NADPH-linked reductase activity for ␣-dicarbonyl compounds, catalyzed the oxidoreduction between xylitol and L-xylulose, and were inhibited competitively by nbutyric acid. Therefore, the proteins are designated as dicarbonyl/L-xylulose reductases (DCXRs). The substrate specificity and kinetic constants of DCXRs for dicarbonyl compounds and sugars are similar to those of mammalian diacetyl reductase and L-xylulose reductase, respectively, and the identity of the DCXRs with these two enzymes was demonstrated by their co-purification from hamster and guinea pig livers and by protein sequencing of the hepatic enzymes. Both DCXR and its mRNA are highly expressed in kidney and liver of human and rodent tissues, and the protein was localized primarily to the inner membranes of the proximal renal tubules in murine kidneys. The results imply that P34H and diacetyl reductase (EC 1.1.1.5) are identical to Lxylulose reductase (EC 1.1.1.10), which is involved in the uronate cycle of glucose metabolism, and the unique localization of the enzyme in kidney suggests that it has a role other than in general carbohydrate metabolism.

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Section: Discussionmentioning

confidence: 51%

Molecular Characterization of Mammalian Dicarbonyl/l-Xylulose Reductase and Its Localization in Kidney

Nakagawa¹,

Ishikura²,

Asami³

et al. 2002

Journal of Biological Chemistry

146

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“…According to these authors (36), the production of acetoin and its subsequent reduction to a diol provides an important mechanism for maintaining the redox balance. This synthetic pathway is also useful because it facilitates a detoxification of acetaldehyde (28,35).…”

Section: Discussionmentioning

confidence: 99%

Effects ofADH2Overexpression inSaccharomyces bayanusduring Alcoholic Fermentation

Maestre

García‐Martínez

Peinado

et al. 2008

Appl Environ Microbiol

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The effect of overexpression of the gene ADH2 on metabolic and biological activity in Saccharomyces bayanus V5 during alcoholic fermentation has been evaluated. This gene is known to encode alcohol dehydrogenase II (ADH II). During the biological aging of sherry wines, where yeasts have to grow on ethanol owing to the absence of glucose, this isoenzyme plays a prominent role by converting the ethanol into acetaldehyde and producing NADH in the process. Overexpression of the gene ADH2 during alcoholic fermentation has no effect on the proteomic profile or the net production of some metabolites associated with glycolysis and alcoholic fermentation such as ethanol, acetaldehyde, and glycerol. However, it affects indirectly glucose and ammonium uptakes, cell growth, and intracellular redox potential, which lead to an altered metabolome. The increased contents in acetoin, acetic acid, and L-proline present in the fermentation medium under these conditions can be ascribed to detoxification by removal of excess acetaldehyde and the need to restore and maintain the intracellular redox potential balance.Saccharomyces cerevisiae possesses at least five genes (ADH1 to ADH5) that encode alcohol dehydrogenase isoenzymes involved in ethanol metabolism. The isoenzymes alcohol dehydrogenase I (ADH I), III, IV, and V reduce acetaldehyde to ethanol during alcoholic fermentation. In contrast, ADH II (EC 1.1.1.1) is glucose repressed and catalyzes the reverse reaction (i.e., the oxidation of ethanol to acetaldehyde). Therefore, when glucose in the fermentation medium is depleted, ADH II is the first enzyme in the use of ethanol (11). S. cerevisiae mutants possessing no ADH activity are unable to grow on ethanol as their sole carbon source, so they tend to accumulate large amounts of glycerol as a result (56). Although ADH1 and ADH2 share 89% sequence similarity, their respective expression products, ADH I and ADH II, differ in affinity for the substrate. Thus, the K m value for ADH II for ethanol is 10 times lower than those for the other ADHs (37). Some authors have studied the presence of various transcription factors for the activation (derepression) of the gene ADH2 (10,13,14,40,43,48,53,55).Once alcoholic fermentation completes and fermentable sugars are depleted, some S. cerevisiae strains can switch from a fermentative metabolism to an oxidative (respiratory) metabolism and form a biofilm known as "flor" on the wine surface (24). Biological aging is carried out by such yeast strains (flor yeasts) (5). The molecular basis for the film formation has been the subject of recent study (19,30,52). During biological aging of wine, flor yeasts grow in a medium containing a high ethanol concentration and produce substantial amounts of acetaldehyde (2). The isoenzyme ADH II plays a key role in this process (6,17,24).Overexpression of the ADH2 gene during fermentation can be expected to create conditions of a futile cycle and affect cellular demands for cofactors and also the redox status of the yeast cells.In order to evaluate the imp...

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“…The subsequent reduction product, butane-2,3-diol, was detected in the liver, kidney and brain. Only 10 minutes incubation time was required to convert 10 nmol (9 x 10 -4 mg) diacetyl to 3.7 nmol (3 x 10 -4 mg) acetoin and 6.3 nmol (6 x 10 -4 mg) butane-2,3-diol in rat liver homogenate (Otsuka et al, 1996). The organspecific reductase activity was greatest in the liver and least in the brain (Otsuka et al, 1996).…”

Section: Iii22 Metabolism Of Aliphatic Acyclic Diketonesmentioning

confidence: 97%

Scientific Opinion on Flavouring Group Evaluation 11, Revision 2 (FGE.11Rev2): Aliphatic dialcohols, diketones, and hydroxyketones from chemical groups 8 and 10

Publication¹

2011

EFS2

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A Detoxication Route for Acetaldehyde: Metabolism of Diacetyl, Acetoin, and 2,3-Butanediol in Liver Homogenate and Perfused Liver of Rats

Cited by 63 publications

References 16 publications

Molecular Characterization of Mammalian Dicarbonyl/l-Xylulose Reductase and Its Localization in Kidney

Molecular Characterization of Mammalian Dicarbonyl/l-Xylulose Reductase and Its Localization in Kidney

Effects ofADH2Overexpression inSaccharomyces bayanusduring Alcoholic Fermentation

Scientific Opinion on Flavouring Group Evaluation 11, Revision 2 (FGE.11Rev2): Aliphatic dialcohols, diketones, and hydroxyketones from chemical groups 8 and 10

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