Moore J W, Babidge W, Millard S, Roediger W E
University of Adelaide, Department of Surgery, Queen Elizabeth Hospital, Woodville, Australia.
Gut. 1997 Jul;41(1):77-81. doi: 10.1136/gut.41.1.77.
It has been proposed that the diminished n-butyrate oxidation observed in ulcerative colitis may be the result of sulphide induced inhibition of short chain acyl-coenzyme A (acyl-CoA) dehydrogenase activity.
To examine the acyl-CoA ester profiles in isolated rat colonic epithelial cells treated in vitro with sodium hydrogen sulphide (NaHS).
Isolated rat colonic epithelial cell suspensions were incubated for 10 minutes in the presence of [1-14C] n-butyrate (5 mM), with and without NaHS (1.5 mM). Incubations were carried out both in the presence and the absence of exogenous CoA and ATP. Metabolic performance was assessed by 14CO2 production and by acyl-CoA ester production measured by HPLC with ultraviolet detection.
Results are given as mean (SEM). For colonocytes incubated in the presence of exogenous CoA and ATP, treatment with NaHS significantly diminished 14CO2 production (control 0.97 (0.06) mumol/g dry weight cells/min, treated 0.26 (0.09) mumol/g dry weight cells/min, p = 0.0019), was associated with an increase in butyryl-CoA concentrations in the final reaction mixture at 10 minutes (control 2.55 (0.28) mumol/g dry weight cells, treated 3.32 (0.32) mumol/g dry weight cells, p = 0.002), and a reduction in crotonyl-CoA concentrations (control 0.274 (0.02) mumol/g dry weight cells, treated 0.120 (0.04) mumol/g dry weight cells, p = 0.008). The mean concentration of acetyl-CoA in the reaction mixture at 10 minutes was not significantly different between control and sulphide treated incubations. There were no significant differences in acyl-CoA ester profiles observed when cells were incubated in the absence of exogenous CoA and ATP.
These results support the view that sulphides inhibit n-butyrate oxidation in colonic epithelial cells by inhibiting short chain acyl dehydrogenation of activated fatty acids.
有人提出，溃疡性结肠炎中观察到的丁酸盐氧化减少可能是硫化物诱导的短链酰基辅酶A（酰基辅酶A）脱氢酶活性抑制的结果。
研究体外经硫化氢钠（NaHS）处理的分离大鼠结肠上皮细胞中的酰基辅酶A酯谱。
将分离的大鼠结肠上皮细胞悬液在[1-¹⁴C]丁酸盐（5 mM）存在下孵育10分钟，分别添加和不添加NaHS（1.5 mM）。在有和没有外源性辅酶A和ATP的情况下进行孵育。通过¹⁴CO₂产生以及通过高效液相色谱-紫外检测法测定的酰基辅酶A酯产生来评估代谢性能。
结果以平均值（标准误）表示。对于在有外源性辅酶A和ATP存在下孵育的结肠细胞，用NaHS处理显著降低了¹⁴CO₂产生（对照0.97（0.06）μmol/克干重细胞/分钟，处理组0.26（0.09）μmol/克干重细胞/分钟，p = 0.0019），与10分钟时最终反应混合物中丁酰辅酶A浓度增加相关（对照2.55（0.28）μmol/克干重细胞，处理组3.32（0.32）μmol/克干重细胞，p = 0.002），以及巴豆酰辅酶A浓度降低（对照0.274（0.02）μmol/克干重细胞，处理组0.120（0.04）μmol/克干重细胞，p = 0.008）。10分钟时反应混合物中乙酰辅酶A的平均浓度在对照和硫化物处理的孵育之间没有显著差异。当细胞在没有外源性辅酶A和ATP的情况下孵育时，观察到的酰基辅酶A酯谱没有显著差异。
这些结果支持以下观点，即硫化物通过抑制活化脂肪酸的短链酰基脱氢作用来抑制结肠上皮细胞中的丁酸盐氧化。
