We have proposed the existence of a bacteriocolonic pathway for ethanol oxidation resulting in high intracolonic levels of toxic and carcinogenic acetaldehyde. This study was aimed at determining the ability of the aldehyde dehydrogenases (ALDH) of aerobic bacteria representing human colonic flora to metabolize intracolonically derived acetaldehyde. The apparent Michaelis constant (Km) values for acetaldehyde were determined in crude extracts of five aerobic bacterial strains, alcohol dehydrogenase (ADH) and ALDH activities of these bacteria at conditions prevailing in the human large intestine after moderate drinking were then compared. The effect of cyanamide, a potent inhibitor of mammalian ALDH, on bacterial ALDH activity was also studied. The apparent Km for acetaldehyde varied from 6.8 (NADP+-linked ALDH of Escherichia coli IH 13369) to 205 microM (NAD+-linked ALDH of Pseudomonas aeruginosa IH 35342), and maximal velocity varied from 6 nmol/min/mg (NAD+-linked ALDH of Klebsiella pneumoniae IH 35385) to 39 nmol/min/mg (NAD+-linked ALDH of Pseudomonas aeruginosa IH 35342). At pH 7.4, and at ethanol and acetaldehyde concentrations that may be prevalent in the human colon after moderate drinking, ADH activity in four out of five bacterial strains were 10-50 times higher than their ALDH activity. Cyanamide inhibited only NAD+-linked ALDH activity of Pseudomonas aeruginosa IH 35342 at concentrations starting from 0.1 nmM. We conclude that ALDHs of the colonic aerobic bacteria are able to metabolize endogenic acetaldehyde. However, the ability of ALDHs to metabolize intracolonic acetaldehyde levels associated with alcohol drinking is rather low. Large differences between ADH and ALDH activities of the bacteria found in this study may contribute to the accumulation of acetaldehyde in the large intestine after moderate drinking. ALDH activities of colonic bacteria were poorly inhibited by cyanamide. This study supports the crucial role of intestinal bacteria in the accumulation of intracolonic acetaldehyde after drinking alcohol. Individual variations in human colonic flora may contribute to the risk of alcohol-related gastrointestinal morbidity.
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http://dx.doi.org/10.1093/oxfordjournals.alcalc.a008391 | DOI Listing |
Microb Cell Fact
April 2024
Department of Food Science and Technology, Texas A&M University, College Station, TX, 77843, USA.
Background: Excessive alcohol consumption has been consistently linked to serious adverse health effects, particularly affecting the liver. One natural defense against the detrimental impacts of alcohol is provided by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), which detoxify harmful alcohol metabolites. Recent studies have shown that certain probiotic strains, notably Lactobacillus spp.
View Article and Find Full Text PDFInt J Mol Sci
June 2023
School of Chemistry and Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
Human aldehyde dehydrogenases (ALDHs) comprising 19 isoenzymes play a vital role on both endogenous and exogenous aldehyde metabolism. This NAD(P)-dependent catalytic process relies on the intact structural and functional activity of the cofactor binding, substrate interaction, and the oligomerization of ALDHs. Disruptions on the activity of ALDHs, however, could result in the accumulation of cytotoxic aldehydes, which have been linked with a wide range of diseases, including both cancers as well as neurological and developmental disorders.
View Article and Find Full Text PDFFront Mol Biosci
May 2021
Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland.
Aldehyde dehydrogenases engage in many cellular functions, however their dysfunction resulting in accumulation of their substrates can be cytotoxic. ALDHs are responsible for the NAD(P)-dependent oxidation of aldehydes to carboxylic acids, participating in detoxification, biosynthesis, antioxidant and regulatory functions. Severe diseases, including alcohol intolerance, cancer, cardiovascular and neurological diseases, were linked to dysfunctional ALDH enzymes, relating back to key enzyme structure.
View Article and Find Full Text PDFBMC Cancer
August 2018
Cancer Research Institute, Biomedical Research Center of Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovakia.
Background: Efficiency of colorectal carcinoma treatment by chemotherapy is diminished as the resistance develops over time in patients. The same holds true for 5-fluorouracil, the drug used in first line chemotherapy of colorectal carcinoma.
Methods: Chemoresistant derivative of HT-29 cells was prepared by long-term culturing in increasing concentration of 5-fluorouracil.
Int J Cancer
September 2016
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
Metabolism reprogramming has been linked with the initiation, metastasis, and recurrence of cancer. The aldehyde dehydrogenase (ALDH) family is the most important enzyme system for aldehyde metabolism. The human ALDH family is composed of 19 members.
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