Clausen M R, Mortensen P B
Department of Medicine A, Rigshospitalet, University of Copenhagen, Denmark.
Gut. 1995 Nov;37(5):684-9. doi: 10.1136/gut.37.5.684.
Short chain fatty acids (SCFAs) are potentially valuable as a topical therapy for distal ulcerative colitis. The mechanism of action is unknown but may involve improved intracellular energy production as previous evidence indicates that colonocyte oxidation of butyrate is impaired in ulcerative colitis. No information is, however, available on human mucosal metabolism of acetate and propionate in either health or disease or the Vmax and Km values of butyrate oxidation. The aim of the study was to assess the kinetic parameters, Vmax and Km, of the complete oxidation of short chain fatty acids and glucose by human colonocytes and to explore whether a metabolic abnormality could be confirmed in patients with ulcerative colitis. Colonocytes were isolated from surgical specimens obtained from 14 patients with ulcerative colitis and eight control subjects. Incubations were performed in the presence of a concentration range of 14C-labelled acetate, propionate butyrate, and glucose. Oxidation rates were obtained by quantifying the production of 14CO2. Vmax and Km were calculated by computer fitting of the data to a Michaelis-Menten plot. No significant differences were shown in either Vmax or Km values of any of the SCFAs or glucose comparing controls and patients with ulcerative colitis. Comparing the results obtained regarding the individual SCFAs, the most striking difference was the considerably lower Km value of butyrate. The apparent Vmax of acetate tended to be higher than Vmax of propionate and butyrate. Vmax of glucose oxidation was significantly lower compared with the Vmax values of SCFA oxidation. The study shows the ability of isolated human colonocytes to utilise each of the three major SCFAs, but does not support a pathogenic role for defective metabolism of butyrate in ulcerative colitis. The considerably lower Km of butyrate oxidation supports a specific role of butyrate as an energy source for the colonic mucosa in both health and ulcerative colitis.
短链脂肪酸（SCFAs）作为远端溃疡性结肠炎的局部治疗方法可能具有重要价值。其作用机制尚不清楚，但可能涉及细胞内能量产生的改善，因为先前的证据表明溃疡性结肠炎中结肠细胞对丁酸盐的氧化受损。然而，关于健康或疾病状态下人类黏膜对乙酸盐、丙酸盐的代谢情况以及丁酸盐氧化的Vmax和Km值，目前尚无相关信息。本研究的目的是评估人类结肠细胞对短链脂肪酸和葡萄糖完全氧化的动力学参数Vmax和Km，并探讨能否在溃疡性结肠炎患者中证实代谢异常。从14例溃疡性结肠炎患者和8例对照受试者的手术标本中分离出结肠细胞。在存在一系列浓度的14C标记的乙酸盐、丙酸盐、丁酸盐和葡萄糖的情况下进行孵育。通过定量14CO2的产生来获得氧化速率。通过将数据拟合到米氏方程曲线，用计算机计算Vmax和Km。比较对照组和溃疡性结肠炎患者，任何一种短链脂肪酸或葡萄糖的Vmax或Km值均无显著差异。比较关于各个短链脂肪酸的结果，最显著的差异是丁酸盐的Km值明显更低。乙酸盐的表观Vmax往往高于丙酸盐和丁酸盐的Vmax。与短链脂肪酸氧化的Vmax值相比，葡萄糖氧化的Vmax显著更低。该研究表明分离出的人类结肠细胞能够利用三种主要短链脂肪酸中的每一种，但不支持丁酸盐代谢缺陷在溃疡性结肠炎中起致病作用。丁酸盐氧化的Km值明显更低，这支持了丁酸盐在健康和溃疡性结肠炎中作为结肠黏膜能量来源的特定作用。
