Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The EXG1 gene encoding the main Saccharomyces cerevisiae exo-beta-1,3-glucanase was cloned and over-expressed in yeast. The Bacillus subtilis endo-1,3-1,4-beta-glucanase gene (beg1) and the Butyrivibrio fibrisolvens endo-beta-1,4-glucanase gene (end1) were fused to the secretion signal sequence of the yeast mating pheromone alpha-factor (MF alpha 1S) and inserted between the yeast alcohol dehydrogenase II gene promoter (ADH2P) and terminator (ADH2T). Constructs ADH2P-MF alpha 1S-beg1-ADH2T and ADH2P-MF alpha 1S-end 1-ADH2T designated BEG1 and END1, respectively, were expressed separately and jointly with EXG1 in S. cerevisiae. The construction of fur 1 ura3 S. cerevisiae strains allowed for the autoselection of these multicopy URA3-based plasmids in rich medium. Enzyme assays confirmed that co-expression of EXG1, BEG1 and END1 enhanced glucan degradation by S. cerevisiae.
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PMID:Over-expression of the Saccharomyces cerevisiae exo-beta-1,3-glucanase gene together with the Bacillus subtilis endo-beta-1,3-1,4-glucanase gene and the Butyrivibrio fibrisolvens endo-beta-1,4-glucanase gene in yeast. 922 61

2-Butoxyethanol, a forestomach carcinogen in mice exposed by inhalation, has been shown to enter the forestomach as a result of grooming and ingestion of material condensed on the skin and fur during exposure. The material entering the stomach concentrates in the forestomach region and persists for at least 48 h post-exposure. Mice given single oral doses of either 2-butoxyethanol or 2-butoxyacetic acid, daily for 10 days, developed a marked hyperkeratosis in the forestomach. 2-Butoxyacetic acid was more potent than 2-butoxyethanol, the NOEL for the former being 50 mg/kg and for the latter, 150 mg/kg. Although a dose dependent increase in cell replication was also seen with both chemicals, the results were confounded by a high labelling rate in the controls. There was no evidence of significant binding of radiolabelled 2-butoxyethanol to proteins in stomach tissues. 2-Butoxyethanol was metabolised in vitro in both mouse and rat forestomach and glandular stomach fractions by alcohol dehydrogenases forming 2-butoxyacetaldehyde which was rapidly converted by aldehyde dehydrogenases to 2-butoxyacetic acid. There was a marked species difference in alcohol dehydrogenase activity between rats and mice with the maximum rates up to one order of magnitude greater in mouse than rat. The alcohol and aldehyde dehydrogenases were heavily concentrated in the stratified squamous epithelium of the forestomach of both rats and mice whereas in the glandular stomach the distribution was more diffuse. In human stomach both enzymes were evenly distributed throughout the epithelial cells of the mucosa. It is concluded that 2-butoxyethanol is ingested following inhalation exposure and concentrates in the forestomach where it is metabolised to 2-butoxyacetic acid which causes cellular damage, increased cell replication and hyperkeratosis. These changes are believed to lead to the tumours seen in mice exposed to 2-butoxyethanol for a lifetime. Differences in structure and enzyme distribution between the rodent and human stomach suggest that the responses seen in the mouse are unlikely to occur in humans.
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PMID:The development of forestomach tumours in the mouse following exposure to 2-butoxyethanol by inhalation: studies on the mode of action and relevance to humans. 1239 95

Poor oral hygiene, ethanol consumption, and human papillomavirus (HPV) are associated with oral and esophageal cancers. However, the mechanism is not fully known. This study examines alcohol metabolism in Streptococcus and its interaction with HPV-16 in the malignant transformation of oral keratinocytes. The acetaldehyde-producing strain Streptococcus gordonii V2016 was analyzed for adh genes and activities of alcohol and aldehyde dehydrogenases. Streptococcus attachment to immortalized HPV-16 infected human oral keratinocytes, HOK (HPV/HOK-16B), human oral buccal keratinocytes, and foreskin keratinocytes was studied. Acetaldehyde, malondialdehyde, DNA damage, and abnormal proliferation among keratinocytes were also quantified. We found that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB, and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol, and ethanol, respectively. S. gordonii V2016 did not show a detectable aldehyde dehydrogenase. AdhE is the major alcohol dehydrogenase in S. gordonii. Acetaldehyde and malondialdehyde production from permissible Streptococcus species significantly increased the bacterial attachment to keratinocytes, which was associated with an enhanced expression of furin to facilitate HPV infection and several malignant phenotypes including acetaldehyde adduct formation, abnormal proliferation, and enhanced migration through integrin-coated basement membrane by HPV-infected oral keratinocytes. Therefore, expression of multiple alcohol dehydrogenases with no functional aldehyde dehydrogenase contributes to excessive production of acetaldehyde from ethanol by oral streptococci. Oral Streptococcus species and HPV may cooperate to transform oral keratinocytes after ethanol exposure. These results suggest a significant clinical interaction, but further validation is warranted.
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PMID:Alcohol metabolism by oral streptococci and interaction with human papillomavirus leads to malignant transformation of oral keratinocytes. 2542 11