Influence of pH on the phase distribution of nascent deoxycholic acid in fresh human cecal aspirates
| Autor: | LA Thomas, R. Hermon Dowling, Martin Veysey, Gerard M. Murphy |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Physiology
medicine.drug_class Centrifugation Suction chemistry.chemical_compound Cholelithiasis Physiology (medical) medicine Distribution (pharmacology) Chemical Precipitation Humans Cecum Colonic disease Hepatology Bile acid Deoxycholic acid Gastroenterology Gallstones Metabolism Hydrogen-Ion Concentration medicine.disease Molecular biology Biochemistry chemistry Intestinal Absorption Solubility Biliary tract Large bowel transit time Colorectal Neoplasms Deoxycholic Acid |
| Zdroj: | American journal of physiology. Gastrointestinal and liver physiology. 281(2) |
| ISSN: | 0193-1857 |
| Popis: | Prolonged large bowel transit time and an associated increase in the proportion of deoxycholic acid (DCA) in serum and bile have been implicated in the development of cholesterol-rich gallstones and colon cancer. Prolongation of intestinal transit also increases intracolonic pH that, we hypothesized, should favor the solubilization and absorption of newly formed DCA within the colon. To test this hypothesis, we performed in vitro studies on homogenized cecal aspirates (obtained at colonoscopy) that were incubated anaerobically with [14C]cholic acid for 16 h after which the pH was adjusted to between 4.0 and 7.0 in 0.5-pH unit steps. The resultant reaction mixtures were centrifuged to separate the supernatant from the precipitate, and the specific activity of [14C]DCA was quantitated in both phases. As the pH in the aspirates was manipulated from 4.0 to 7.0, the proportion of newly formed, labeled DCA increased in the supernatant and fell in the precipitate, particularly at a hydrogen ion concentration of −7(equivalent to pH 5.0–7.0). These results show that the solubility of DCA in colonic contents increases with increasing pH. If solubility is rate limiting, this should lead to increased absorption that, in turn, would explain why the proportion of DCA in serum and bile increases with the prolongation of large bowel transit time. |
| Databáze: | OpenAIRE |
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