Disease relevance of acetaldehyde

• Potentially, the development of newer drugs that selectively inhibit AR-mediated glucose metabolism and signaling, without affecting aldehyde detoxification, may be useful in preventing inflammation associated with the development of diabetic complications, particularly micro- and macrovascular diseases [1].
• The crystal structure of the aldehyde oxido-reductase (Mop) from the sulfate reducing anaerobic Gram-negative bacterium Desulfovibrio gigas has been determined at 2.25 A resolution by multiple isomorphous replacement and refined [2].
• The effects of ethanol and acetaldehyde on the response of actomyosin to ADP may play a role in the pathogenesis of alcoholic myopathy and cardiomyopathy [3].
• Aldehyde dehydrogenase may be involved in the detoxification of acetaldehyde produced by ethanolic fermentation during pollen development, may play a role in energy metabolism, or may interact with URF13, the mitochondrial protein associated with male sterility in cmsT maize [4].
• Cocultures of HIV-infected monocytes and neuroblastoma or endothelial cells, or HIV-infected monocyte fluids, sucrose gradient-concentrated viral particles, and paraformaldehyde-fixed or freeze-thawed HIV-infected monocytes placed onto astroglia failed to induce cytokines and neuronotoxins [5].

Psychiatry related information on acetaldehyde

• A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism [6].
• Immunohistochemical demonstration of acetaldehyde-modified epitopes in human liver after alcohol consumption [7].
• The data strongly suggest that genetic variation in both ADH and ALDH may influence drinking behavior and the risk of alcoholism developing through acetaldehyde formation [8].
• Aldehyde excretion is influenced by numerous factors that affect the formation of lipid peroxides in vivo such as energy status, physical activity and environmental temperature, as well as by wide variations in the intake of peroxides in the diet [9].
• BACKGROUND: The mutant allele of mitochondrial aldehyde dehydrogenase (ALDH2(*)2) was found to be associated with Alzheimer's disease (AD) in a Japanese sample, interacting with the apolipoprotein E epsilon 4 allele (Apo E4) [10].

High impact information on acetaldehyde

• The MEOS was purified and reconstituted using 2E1, phospholipids, and cytochrome P-450 reductase and shown to oxidize ethanol to acetaldehyde, mainly as a monooxygenase and secondarily via hydroxyl radicals, with transcriptional and posttranscriptional regulation [11].
• Pyruvate loses carbon dioxide to produce acetaldehyde, which is reduced by alcohol dehydrogenase 1 (Adh1) to ethanol, which accumulates [12].
• Here, we report the crystal structures of the 40 kDa catalytic core domain of HAUSP in isolation and in complex with ubiquitin aldehyde [13].
• Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde [13].
• Binding by ubiquitin aldehyde induces a drastic conformational change in the active site that realigns the catalytic triad residues for catalysis [13].

Chemical compound and disease context of acetaldehyde

• This apparently contradictory finding is rationalized in terms of the subsequent enzymatic oxidation of acetaldehyde to acetic acid, which was previously regarded as the volatile fragment released by the action of the biosynthetic enzymes of Propionibacterium shermanii [14].
• X-ray crystallographic data show that a specific tetrapeptide aldehyde inhibitor (N-acetylprolylalanylprolylphenylalaninal) forms a stable, covalent, tetrahedral addition complex with the serine protease, SGPA, from Streptomyces griseus [15].
• The selective toxicity of cyclophosphamide is due, at least in part, to a greater expression of the relevant aldehyde dehydrogenase activity in normal cells relative to that expressed in certain tumor cells [16].
• Measurement of activity and immunoblot results showed that ALDH2 and ATP synthase were also inhibited through oxidative modification of their cysteine or tyrosine residues in alcoholic fatty livers of rats [17].
• When monocytes were treated with any type of IFN for 16 h, and then fixed with paraformaldehyde, they did not show cytotoxicity to A375 cells, but when they were fixed after treatment with norMDP or lipopolysaccharide they showed significant cytotoxicity to A375 melanoma cells [18].

Biological context of acetaldehyde

• A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death [19].
• Product aldehyde inhibits the hydrolysis, making release of product the rate-determining step of the reaction in the crystal [20].
• Eliciting the low-activity aldehyde dehydrogenase Asian phenotype by an antisense mechanism results in an aversion to ethanol [6].
• Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant [21].
• RESULTS: Exposure to ethanol or acetaldehyde led to cell activation and intracellular lipid peroxidation [22].

Anatomical context of acetaldehyde

• They also suggest that acetaldehyde has a role in ethanol-mediated bone-marrow suppression [23].
• Spleen colony formation by pluripotent stem cells was resistant to concentrations of ethanol and acetaldehyde that suppressed in vitro colony formation of committed myeloid and erythroid progenitor cells by 50 per cent [23].
• The reduced ability of mitochondria to metabolize acetaldehyde may explain the high levels of acetaldehyde in the blood of alcoholics, which in turn could promote the perpetuation of liver injury [24].
• Prolonged consumption of ethanol significantly reduces the capacity of rat liver mitochondria to oxidize acetaldehyde [24].
• Other aliphatic alcohols such as propanol and butanol also significantly augmented PA production and secretion by endothelial cells, whereas acetaldehyde and acetylcoenzyme A, known metabolites of ethyl alcohol, had no stimulatory effect on protease secretion by the cells [25].

Associations of acetaldehyde with other chemical compounds

• Immunization with transition state analogue 1 results in a germline-encoded antibody that catalyses the rearrangement of hexadiene 2 to aldehyde 3 with a rate approaching that of a related pericyclic reaction catalysed by the enzyme chorismate mutase [26].
• The antibodies use the epsilon-amino group of Lys to form an enamine with ketone substrates and use this enamine as a nascent carbon nucleophile to attack the second substrate, an aldehyde, to form a new carbon-carbon bond [27].
• Crystal structure of the xanthine oxidase-related aldehyde oxido-reductase from D. gigas [2].
• Brefeldin A, gelonin, and a peptide aldehyde inhibitor of proteasomal processing each blocked presentation of macropinocytosed antigen, demonstrating that unusual access to the conventional class I MHC pathway was occurring [28].
• DV-monocytes fixed with paraformaldehyde or glutaraldehyde, which produced no infectious virus, also induced high levels of IFN from PBL [29].
• The second pathway is inducible and involves the microsomal ethanol-oxidizing system (MEOS), in which the oxidation of ethanol to acetaldehyde and acetic acid also leads to generation of reactive oxygen species (ROS) [30].

Gene context of acetaldehyde

• Deficiency in mitochondrial aldehyde dehydrogenase (ALDH2), a tetrameric enzyme, results from inheriting one or two ALDH2*2 alleles [31].
• Adding PON to HDL prolonged the oxidation lag phase and reduced HDL peroxide and aldehyde formation by up to 95% [32].
• Here, we report the crystal structures of the 45-kDa catalytic domain of USP14 in isolation and in a complex with ubiquitin aldehyde, which reveal distinct structural features [33].
• This screen yielded a number of genes not previously implicated in salt stress, including ALD6, which encodes an NADP(+)-dependent aldehyde dehydrogenase, and UTR1, which encodes an NAD+ kinase [34].
• Ac-Tyr-Val-Ala-Asp-amino-4-methyl coumarin, patterned after site 2 of human pIL-1 beta, is a fluorogenic substrate for mICE, while the tetrapeptide aldehyde Ac-Tyr-Val-Ala-Asp-CHO is a potent inhibitor (Ki = 3 nM) that prevents generation and release of mature IL-1 beta by PECs (IC50 = 7 microM) [35].

Analytical, diagnostic and therapeutic context of acetaldehyde

• We report here that intravenous injection of paraformaldehyde-fixed autologous cells infected in vitro with V25 (individual D.Z.) gave the best results [36].
• At low infusion dosage when the EEG was unaffected, concentrations of acetaldehyde in the blood were equal to or greater than those which occur during intoxication [37].
• Using an antiserum specific for MDA-lysine protein adducts, we demonstrated by immunohistochemistry the presence of aldehyde-protein adducts in the cytosol of periportal hepatocytes, which co-localized with iron [38].
• Maximum protection was achieved by vaccination with live FL74 cells or with a low dose of freeze-thawed cells, but tumor cells inactivated by glutaraldehyde or paraformaldehyde were also effective [39].
• The sphincter and the esophageal body were identified manometrically and fixed in situ by perfusion with aldehyde fixative [40].

References