Characteristics of aldehyde dehydrogenases of certain aerobic bacteria representing human colonic flora.
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.
Nosova
T
T
Research Unit of Alcohol Diseases, University Central Hospital of Helsinki, Finland.
Jokelainen
K
K
Kaihovaara
P
P
Heine
R
R
Jousimies-Somer
H
H
Salaspuro
M
M
D000079:Acetaldehyde / Q000378:metabolism* / Q000633:toxicity; D000428:Alcohol Drinking / Q000009:adverse effects; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D003106:Colon / Q000201:enzymology / Q000382:microbiology*; D004926:Escherichia coli / Q000201:enzymology*; D000431:Ethanol / Q000493:pharmacokinetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000201:enzymology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D012307:Risk Factors
D000431:Ethanol; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde