Nosova T, Jokelainen K, Kaihovaara P, Heine R, Jousimies-Somer H, Salaspuro M
Research Unit of Alcohol Diseases, University Central Hospital of Helsinki, Finland.
Alcohol Alcohol. 1998 May-Jun;33(3):273-80. doi: 10.1093/oxfordjournals.alcalc.a008391.
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.
我们提出存在一条乙醇氧化的细菌 - 结肠途径,该途径会导致结肠内有毒和致癌的乙醛水平升高。本研究旨在确定代表人类结肠菌群的需氧菌的乙醛脱氢酶(ALDH)代谢结肠内源性乙醛的能力。在五种需氧细菌菌株的粗提物中测定乙醛的表观米氏常数(Km)值,然后比较这些细菌在适度饮酒后人类大肠中普遍存在的条件下的乙醇脱氢酶(ADH)和ALDH活性。还研究了氰胺(一种有效的哺乳动物ALDH抑制剂)对细菌ALDH活性的影响。乙醛的表观Km值从6.8(大肠杆菌IH 13369的NADP + 连接的ALDH)到205微摩尔(铜绿假单胞菌IH 35342的NAD + 连接的ALDH)不等,最大反应速度从6纳摩尔/分钟/毫克(肺炎克雷伯菌IH 35385的NAD + 连接的ALDH)到39纳摩尔/分钟/毫克(铜绿假单胞菌IH 35342的NAD + 连接的ALDH)不等。在pH 7.4以及适度饮酒后人类结肠中可能普遍存在的乙醇和乙醛浓度下,五株细菌中有四株的ADH活性比其ALDH活性高10 - 50倍。氰胺仅在浓度从0.1纳摩尔开始时抑制铜绿假单胞菌IH 35342的NAD + 连接的ALDH活性。我们得出结论,结肠需氧菌的ALDH能够代谢内源性乙醛。然而,ALDH代谢与饮酒相关的结肠内乙醛水平的能力相当低。本研究中发现的细菌的ADH和ALDH活性之间的巨大差异可能导致适度饮酒后大肠中乙醛的积累。结肠细菌的ALDH活性受氰胺的抑制作用较弱。本研究支持肠道细菌在饮酒后结肠内乙醛积累中的关键作用。人类结肠菌群的个体差异可能导致与酒精相关的胃肠道疾病风险增加。