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Intestinal Transport of Bile Acids

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Abstract

The sections in this article are:

1 Rate Determinants of Intestinal Bile Acid Transport
1.1 Passive Absorption from Monomer Solutions
1.2 Passive Absorption from Micellar Solutions
1.3 Carrier‐Mediated Absorption
2 Mechanisms of Cellular Bile Acid Transport
2.1 General Characteristics
2.2 Major Site for Bile Acid Absorption
2.3 Structure‐Activity Relationships
2.4 Membrane Site for Active Transport
2.5 Sodium—Bile Acid Cotransport System
2.6 Cellular Metabolism and Exit of Bile Acids
3 Ontogenesis of Bile Acid Transport
4 Summary
Figure 1. Figure 1.

Structure of cholic, glycocholic, and taurocholic acids. Fusion of A/B ring is in cis‐configuration. Hydroxyl groups are at positions 3α, 7α, and 12α on steroid nucleus. Bile acids are unconjugated or conjugated with the amino acids glycine or taurine.

Figure 2. Figure 2.

Relationship of apparent permeability coefficients, *P, for ionized () and protonated (·) bile acids to their hydrogen‐bonding capability. *P has been multiplied by square root of molecular weight (M0.5) for each bile acid, and ln of product has been plotted against the number (N) of hydrogen bonds that a particular bile acid can form in water.

[From Wilson and Dietschy 120.]
Figure 3. Figure 3.

Theoretical relationship between kinetics of active transport and variations in unstirred layer thickness, diffusivity of probe molecule, and uptake rates. Active transport kinetics are altered by changes in thickness (d) of unstirred water layer (panel A), by changes in free diffusion coefficient (D) of probe molecule (panel B), and by changes in absolute flux rate (J) across unstirred layer (panel C). Jmax, true maximal transport rate for membrane carrier; Km, Michaelis constant for membrane carrier; *Km, apparent Michaelis constant. Panel A, d is varied; Jmax, 4 nmol · s−1 · cm−1; Km, 1 mM; D, 0.5 × 10−5 cm2/s. Panel B, D is varied; Jmax, 4 nmol · s−1 · cm−2; Km, 1 mM; d, 1 × 10−2 cm. Panel C, Jmax and therefore J are varied; Km, 1 mM; d, 1 × 10−2 cm; D, 0.5 × 10−5 cm2/s. Hypothetical membrane is considered to be flat and of known surface area so that flux rates (J) are in nmol · s−1 · cm−2; hence the surface area of the UWL (SW), which is used to correct experimentally determined flux rates (Jd to J), does not enter into calculations.

[From Wilson and Dietschy 121.]
Figure 4. Figure 4.

Distribution of radioactivity after sodium dodecyl sulfate—polyacrylamide gel electrophoresis of ileal brush‐border membrane vesicles after photoaffinity labeling with 3‐azido bile acid derivatives. Membrane vesicles (0.5 mg of protein) photolabeled in the presence of 1.5 μM (5.5 μCi) 3‐azido‐taurocholic acid (top) or 7.45 μM (6.05 μCi) 3‐azido‐cholic acid (bottom). Total acrylamide concentration, 9%. Arrow, position of bromophenol blue; solid line, densitometer scanning of polypeptides after staining; broken lines, distribution of radioactivity.

[From Kramer et al. 48.]
Figure 5. Figure 5.

Kinetics of taurocholic acid transport in vesicles prepared from 2‐wk‐, 3‐wk‐, and 6‐wk‐old rats. Ileal membrane vesicles were preloaded with 100 mM mannitol, 100 mM choline chloride or Na+ chloride, 20 mM HEPES‐TRIS (pH 7.4), and unlabeled taurocholic acid at indicated concentrations. Incubations (37°C, 120 s) were initiated in identical solution excepting presence of tracer amounts of [3H]taurocholic acid and 6 μg gramicidin/mg protein. Data points, arithmetic difference ± SE of the difference between tracer uptake in presence of Na+‐preequilibrated and choline‐preequilibrated conditions (n = 8, where n is the number of determinations).

[From Barnard and Ghishan 5.]
Figure 6. Figure 6.

Schematic representation of intestinal bile acid transport. Bile acid monomers and micelles diffuse from bulk phase (C1) across unstirred water layer (UWL) and acidic microclimate of thickness (d) and surface area (SW) to aqueous‐membrane interface at C2. Bile acid monomers are transported across brush‐border membrane either by passive diffusion throughout intestine or by active transport in ileum. Ileal recognition site contains a steroid recognition component, a positive charge to react with negatively charged bile acid side chain, and an anionic site to interact with Na+. Energy for active transport arises from Na+ gradient across brush‐border membrane. Low intracellular Na+ concentration necessary for continued operation of system is maintained through Na+‐K+ exchange by ATPase located on basolateral membrane. Route and mechanisms responsible for transcellular transport of bile acids remain unknown. Exit of bile acids may involve transport down an electrochemical gradient, anion exchange, and other yet‐to‐be‐defined transport systems.

[From Wilson 116.]


Figure 1.

Structure of cholic, glycocholic, and taurocholic acids. Fusion of A/B ring is in cis‐configuration. Hydroxyl groups are at positions 3α, 7α, and 12α on steroid nucleus. Bile acids are unconjugated or conjugated with the amino acids glycine or taurine.



Figure 2.

Relationship of apparent permeability coefficients, *P, for ionized () and protonated (·) bile acids to their hydrogen‐bonding capability. *P has been multiplied by square root of molecular weight (M0.5) for each bile acid, and ln of product has been plotted against the number (N) of hydrogen bonds that a particular bile acid can form in water.

[From Wilson and Dietschy 120.]


Figure 3.

Theoretical relationship between kinetics of active transport and variations in unstirred layer thickness, diffusivity of probe molecule, and uptake rates. Active transport kinetics are altered by changes in thickness (d) of unstirred water layer (panel A), by changes in free diffusion coefficient (D) of probe molecule (panel B), and by changes in absolute flux rate (J) across unstirred layer (panel C). Jmax, true maximal transport rate for membrane carrier; Km, Michaelis constant for membrane carrier; *Km, apparent Michaelis constant. Panel A, d is varied; Jmax, 4 nmol · s−1 · cm−1; Km, 1 mM; D, 0.5 × 10−5 cm2/s. Panel B, D is varied; Jmax, 4 nmol · s−1 · cm−2; Km, 1 mM; d, 1 × 10−2 cm. Panel C, Jmax and therefore J are varied; Km, 1 mM; d, 1 × 10−2 cm; D, 0.5 × 10−5 cm2/s. Hypothetical membrane is considered to be flat and of known surface area so that flux rates (J) are in nmol · s−1 · cm−2; hence the surface area of the UWL (SW), which is used to correct experimentally determined flux rates (Jd to J), does not enter into calculations.

[From Wilson and Dietschy 121.]


Figure 4.

Distribution of radioactivity after sodium dodecyl sulfate—polyacrylamide gel electrophoresis of ileal brush‐border membrane vesicles after photoaffinity labeling with 3‐azido bile acid derivatives. Membrane vesicles (0.5 mg of protein) photolabeled in the presence of 1.5 μM (5.5 μCi) 3‐azido‐taurocholic acid (top) or 7.45 μM (6.05 μCi) 3‐azido‐cholic acid (bottom). Total acrylamide concentration, 9%. Arrow, position of bromophenol blue; solid line, densitometer scanning of polypeptides after staining; broken lines, distribution of radioactivity.

[From Kramer et al. 48.]


Figure 5.

Kinetics of taurocholic acid transport in vesicles prepared from 2‐wk‐, 3‐wk‐, and 6‐wk‐old rats. Ileal membrane vesicles were preloaded with 100 mM mannitol, 100 mM choline chloride or Na+ chloride, 20 mM HEPES‐TRIS (pH 7.4), and unlabeled taurocholic acid at indicated concentrations. Incubations (37°C, 120 s) were initiated in identical solution excepting presence of tracer amounts of [3H]taurocholic acid and 6 μg gramicidin/mg protein. Data points, arithmetic difference ± SE of the difference between tracer uptake in presence of Na+‐preequilibrated and choline‐preequilibrated conditions (n = 8, where n is the number of determinations).

[From Barnard and Ghishan 5.]


Figure 6.

Schematic representation of intestinal bile acid transport. Bile acid monomers and micelles diffuse from bulk phase (C1) across unstirred water layer (UWL) and acidic microclimate of thickness (d) and surface area (SW) to aqueous‐membrane interface at C2. Bile acid monomers are transported across brush‐border membrane either by passive diffusion throughout intestine or by active transport in ileum. Ileal recognition site contains a steroid recognition component, a positive charge to react with negatively charged bile acid side chain, and an anionic site to interact with Na+. Energy for active transport arises from Na+ gradient across brush‐border membrane. Low intracellular Na+ concentration necessary for continued operation of system is maintained through Na+‐K+ exchange by ATPase located on basolateral membrane. Route and mechanisms responsible for transcellular transport of bile acids remain unknown. Exit of bile acids may involve transport down an electrochemical gradient, anion exchange, and other yet‐to‐be‐defined transport systems.

[From Wilson 116.]
References
 1. Abberger, H., H.‐P. Busher, K. Fuchte, W. Gerok, U. Giese, W. Kramer, G. Kurz, and U. Zanger. Compartmentation of bile salt biosynthesis and transport revealed by photoaffinity labelling of isolated hepatocytes. In: Bile Acids and Cholesterol in Health and Disease, edited by G. Paumgartner, A. Stiehl, and W. Gerok. Lancaster, UK: MTP, 1983, p. 77–87.
 2. Angelin, B., K. Einarsson, and K. Hellstrom. Evidence for the absorption of bile acids in the proximal small intestine of normo‐ and hyperlipidaemic subjects. Gut 17: 420–425, 1976.
 3. Armstrong, M. J., and M. C. Carey. The hydrophobic‐hydrophilic balance of bile salts. Inverse correlation between reverse‐phase high performance liquid chromatographic mobilities and micellar cholesterol‐solubilizing capacities. J. Lipid Res. 23: 70–80, 1982.
 4. Barnard, J. A., and F. K. Ghishan. Taurocholate transport by human ileal brush border membrane vesicles (Abstract). Gastroenterology 90: A1336, 1986.
 5. Barnard, J. A., and F. K. Ghishan. Methylprednisolone accelerates the ontogeny of sodium taurocholate cotransport in rat ileal brush border membranes. J. Lab. Clin. Med. 108: 549–555, 1986.
 6. Barnard, J. A., F. K. Ghishan, and F. A. Wilson. Ontogenesis of taurocholate transport by rat ileal brush border membrane vesicles. J. Clin. Invest. 75: 869–873, 1985.
 7. Beesley, R. C., and R. G. Faust. Sodium ion‐coupled uptake of taurocholate by intestinal brush‐border membrane vesicles. Biochem. J. 178: 299–303, 1979.
 8. Beesley, R. C., and R. G. Faust. Bile‐salt inhibition of sodium ion‐coupled d‐glucose and l‐alanine accumulation by brush‐border membrane vesicles from hamster jejunum. Biochem. J. 190: 731–736, 1980.
 9. Borgström, B. The micellar hypothesis of fat absorption: must it be revisited? Scand. J. Gastroenterol. 20: 389–394, 1985.
 10. Bundy, R., J. Mauskopf, J. T. Walker, and L. Lack. Interaction of uncharged bile salt derivatives with the ileal bile salt transport system. J. Lipid Res. 18: 389–395, 1977.
 11. Burckhardt, G., W. Kramer, G. Kurz, and F. A. Wilson. Inhibition of bile salt transport in brush‐border membrane vesicles from rat small intestine by photoaffinity labeling. J. Biol. Chem. 258: 3618–3622, 1983.
 12. Carey, M. C., and D. M. Small. Micelle formation by bile salts. Arch. Intern. Med. 130: 506–527, 1972.
 13. Chowdhry, V., and F. H. Westheimer. Photoaffinity labeling of biological systems. Annu. Rev. Biochem. 48: 293–325, 1979.
 14. Crane, R. K. Hypothesis for mechanism of intestinal active transport of sugars. Federation Proc. 21: 891–895, 1962.
 15. Crane, R. K. Na+‐dependent transport in the intestine and other animal tissues. Federation Proc. 24: 1000–1006, 1965.
 16. Crane, R. K. The gradient hypothesis and other models of carrier‐mediated active transport. Rev. Physiol. Biochem. Pharmacol. 78: 101–119, 1977.
 17. DeBelle, R. C., V. Vaupshas, B. B. Vitullo, L. R. Haber, E. Shaffer, G. G. Mackie, H. Owen, J. M. Little, and R. Lester. Intestinal absorption of bile salts: immature development in the neonate. J. Pediatr. 94: 472–476, 1979.
 18. Diamond, J. M., and E. M. Wright. Biological membranes: the physical basis of ion and nonelectrolyte selectivity. Annu. Rev. Physiol. 31: 581–646, 1969.
 19. Dietschy, J. M. Mechanisms for the intestinal absorption of bile acids. J. Lipid Res. 9: 297–309, 1968.
 20. Dietschy, J. M., H. S. Salomon, and M. D. Siperstein. Bile acid metabolism. I. Studies on the mechanisms of intestinal transport. J. Clin. Invest. 45: 832–846, 1966.
 21. Farivar, S., H. Fromn, D. Schindler, B. McJunkin, and F. W. Schmidt. Tests of bile acid and vitamin B12 metabolism in ileal Crohn's disease. Am. J. Clin. Pathol. 73: 69–74, 1980.
 22. Feldman, E. B. Physiochemical processes in sterol absorption. Biochem. Med. 2: 136–144, 1968.
 23. Firpi, A., J. T. Walker, and L. Lack. Interactions of cationic bile salt derivatives with the ileal bile salt transport system. J. Lipid Res. 16: 379–385, 1975.
 24. Fondacaro, J. D. Influence of dietary lipids on intestinal bile acid absorption. Proc. Soc. Exp. Biol. Med. 173: 118–124, 1983.
 25. Fondacaro, J. D., and J. B. Rodgers. Characterization and effect of phospholipid on bile acid absorption by villi isolated from hamster small intestine. Am. J. Dig. Dis. 23: 12–17, 1978.
 26. Frohling, W., and A. Stiehl. Bile salt glucuronides: identification and quantitative analysis in the urine of patients with cholestasis. Eur. J. Clin. Invest. 6: 67–74, 1976.
 27. Gallagher, K., J. Mauskopf, J. T. Walker, and L. Lack. Ionic requirements for the active ileal bile salt transport system. J. Lipid Res. 17: 572–577, 1976.
 28. Hagenbuch, G., G. Stange, and H. Murer. Transport of sulfate in rat jejunal and rat proximal tubular basolateral membrane vesicles. Pfluegers Arch. 405: 202–208, 1985.
 29. Heaton, K. W., and L. Lack. Ileal bile salt transport: mutual inhibition in an in vivo system. Am. J. Physiol. 214: 585–590, 1968.
 30. Henderson, P. J. F., J. D. McGivan, and J. B. Chapell. The action of certain antibiotics on mitochondrial, erythrocyte and artificial phospholipid membranes. Biochem. J. 111: 521–535, 1969.
 31. Heubi, J. E., and J. L. Fellows. Postnatal development of intestinal bile salt transport. Relationship to membrane physico‐chemical changes. J. Lipid Res. 26: 797–805, 1985.
 32. Heubi, J. E., and J. D. Fondacaro. Postnatal development of intestinal bile salt transport in the guinea pig. Am. J. Physiol. 243 (Gastrointest. Liver Physiol. 6): G189–G194, 1982.
 33. Hoffman, N. E., and V. J. Yeoh. The relationship between concentration and uptake by rat small intestine in vitro for two micellar solutes. Biochim. Biophys. Acta 233: 49–52, 1971.
 34. Hofmann, A. F. The enterohepatic circulation of bile acids in man. In: Advances in Internal Medicine, edited by G. H. Stollerman Chicago, IL: Year Book, 1976, vol. 21, p. 501–533.
 35. Hofmann, A. F., and S. A. Cummings. Measurement of bile acid and cholesterol kinetics in man by isotope dilution: principles and applications. In: Bile Acids in Gastroenterology, edited by E. Roda Hingham, MA: MTP, 1983, p. 75–117.
 36. Hofmann, A. F., and J. R. Poley. Role of bile acid malabsorption in pathogenesis of diarrhea and steatorrhea in patients with ileal resection. Gastroenterology 62: 918–934, 1972.
 37. Hofmann, A. F., and A. Roda. Physicochemical properties of bile acids and their relationship to biological properties: an overview of the problem. J. Lipid Res. 25: 1477–1489, 1984.
 38. Holt, P. R. Intestinal absorption of bile salts in the rat. Am. J. Physiol. 207: 1–7, 1964.
 39. Holt, P. R. Competitive inhibition of intestinal bile salt absorption in the rat. Am. J. Physiol. 210: 635–639, 1966.
 40. Honkanen, R. E., M. W. Rigler, and J. S. Patton. Dietary fat assimilation and bile salt absorption in the killifish intestine. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G399–G407, 1985.
 41. Hosang, M., A. Vasella, and G. Semenza. Specific photoaffinity inactivation of the d‐glucose transporter in small intestinal brush border membrane using new phlorizin analogues. Biochemistry 20: 5844–5854, 1981.
 42. Hurwitz, S. A., A. Bar, M. Katz, D. Sklan, and P. Budowski. Absorption and secretion of fatty acids and bile acids in the intestine of the laying fowl. J. Nutr. 103: 543–547, 1973.
 43. Kern, F., and B. Borgström. The effect of a conjugated bile salt on oleic acid absorption in the rat. Gastroenterology 49: 623–631, 1965.
 44. Kessler, M., and G. Semenza. The small‐intestinal Na+, d‐glucose cotransporter: an asymmetric gated channel (or pore) response to ΔΨ. J. Membr. Biol. 76: 27–56, 1983.
 45. Knoebel, L. K., and J. M. Ryan. Digestion and mucosal absorption of fat in normal and bile‐deficient dogs. Am. J. Physiol. 204: 509–514, 1963.
 46. Krag, E., and S. F. Phillips. Active and passive bile acid absorption in man. J. Clin. Invest. 53: 1686–1694, 1974.
 47. Kramer, W., U. Bickel, H.‐P. Buscher, W. Gerok, and G. Kurz. Bile‐salt‐binding polypeptides in plasma membranes of hepatocytes revealed by photoaffinity labelling. Eur. J. Biochem. 129: 13–24, 1982.
 48. Kramer, W., G. Burckhardt, F. A. Wilson, and G. Kurz. Bile salt‐binding polypeptides in brush‐border membrane vesicles from rat small intestine revealed by photoaffinity labeling. J. Biol. Chem. 258: 3623–3627, 1983.
 49. Kramer, W., H.‐P. Buscher, W. Gerok, and G. Kurz. Bile salt binding to serum components. Eur. J. Biochem. 102: 1–9, 1979.
 50. Kurtin, P., and A. N. Charney. Intestinal ion transport and intracellular pH during acute respiratory alkalosis and acidosis. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G24–G31, 1984.
 51. Lack, L. Properties and biological significance of the ileal bile salt transport system. Environ. Health Perspect. 33: 79–90, 1979.
 52. Lack, L., A. Tantawi, C. Halevy, and D. Rockett. Positional requirements for anionic charge for ileal absorption of bile salt analogues. Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G745–G749, 1984.
 53. Lack, L., J. T. Walker, and C.‐Y. H. Hsu. Taurocholate uptake by membrane vesicles prepared from ileal brush borders. Life Sci. 20: 1607–1611, 1977.
 54. Lack, L., J. T. Walker, and G. D. Singletary. Ileal bile salt transport: in vivo studies of effect of substrate ionization on activity. Am. J. Physiol. 219: 487–490, 1970.
 55. Lack, L., and I. M. Weiner. In vitro absorption of bile salts by small intestine of rats and guinea pigs. Am. J. Physiol. 200: 313–317, 1961.
 56. Lack, L., and I. M. Weiner. Intestinal bile salt transport: structure‐activity relationships and other properties. Am. J. Physiol. 210: 1142–1152, 1966.
 57. Lack, L., and I. M. Weiner. The ileal bile salt transport system: effect of the charged state of the substrate on activity. Biochim. Biophys. Acta 135: 1065–1068, 1967.
 58. Lester, R., R. A. Smallwood, J. M. Little, A. S. Brown, G. J. Piasecki, and B. T. Jackson. Fetal bile salt metabolism. The intestinal absorption of bile salt. J. Clin. Invest. 59: 1009–1016, 1977.
 59. Lester, R., J. Pyrek, J. M. Little, and E. W. Adcock. What is meant by the term “bile acid”? Am. J. Physiol. 244 (Gastrointest. Liver Physiol. 7): G107–G110, 1983.
 60. Little, J. M., and R. Lester. Ontogenesis of intestinal bile salt absorption in the neonatal rat. Am. J. Physiol. 239 (Gastrointest. Liver Physiol. 2): G319–G323, 1980.
 61. Low‐Beer, T. S., M. P. Tyor, and L. Lack. Effects of sulfation of taurolithocholic and glycolithocholic acids on their intestinal transport. Gastroenterology 56: 721–726, 1969.
 62. Lucas, M. Determination of acid surface pH in vivo in rat proximal jejunum. Gut 24: 734–739, 1983.
 63. Lücke, H., G. Stange, R. Kinne, and H. Murer. Taurocholate—sodium co‐transport by brush‐border membrane vesicles isolated from rat ileum. Biochem. J. 174: 951–958, 1978.
 64. Matern, S., and W. Gerok. Pathophysiology of the enterohepatic circulation of bile acids. Rev. Physiol. Biochem. Pharmacol. 85: 125–204, 1979.
 65. Matern, S., H. Matern, E. H. Farthmann, and W. Gerok. Hepatic and extrahepatic glucuronidation of bile acids in man. J. Clin. Invest. 74: 402–410, 1984.
 66. McClintock, C., and Y.‐F. Shiau. Jejunum is more important than terminal ileum for taurocholate absorption in rats. Am. J. Physiol. 244 (Gastrointest. Liver Physiol. 7): G507–G514, 1983.
 67. Moyer, M. S., J. E. Heubi, A. L. Goodrich, W. F. Balisteri, and F. Suchy. Ontogeny of bile acid transport in brush border membrane vesicles from rat ileum. Gastroenterology 90: 1188–1196, 1986.
 68. Palmer, R. H. The formation of bile acid sulfates: a new pathway of bile acid metabolism in humans. Proc. Natl. Acad. Sci. USA 58: 1047–1050, 1967.
 69. Parquet, M., M. Pessah, E. Sacquet, C. Salvat, A. Raizman, and R. Infante. Glucuronidation of bile acids in human liver, intestine and kidney. FEBS Lett. 189: 183–187, 1985.
 70. Patton, J. S. Gastrointestinal lipid digestion. In: Physiology of the Gastrointestinal Tract, edited by L. R. Johnson New York: Raven, 1981, vol. 2, p. 1123–1146.
 71. Playoust, M. R., and K. J. Isselbacher. Studies on the transport and metabolism of conjugated bile salts by intestinal mucosa. J. Clin. Invest. 43: 467–476, 1964.
 72. Playoust, M. R., L. Lack, and I. M. Weiner. Effect of intestinal resection on bile salt absorption in dogs. Am. J. Physiol. 208: 363–369, 1965.
 73. Pressman, B. C. Ionophorous antibiotics as models for biological transport. Federation Proc. 27: 1283–1288, 1968.
 74. Proulx, P., H. Aubry, I. Brglez, and D. G. Williamson. The effect of phosphoglycerides on the incorporation of cholesterol into isolated brush‐border membranes from rabbit small intestine. Biochim. Biophys. Acta 775: 341–346, 1984.
 75. Proulx, P., H. Aubry, I. Brglez, and D. G. Williamson. Studies on the mechanism of cholesterol uptake and on the effects of bile salt in this uptake by brush‐border membranes isolated from rabbit small intestine. Biochim. Biophys. Acta 778: 586–593, 1984.
 76. Rachmilewitz, D., and D. R. Saunders. Metabolism of chenodeoxycholate by intestinal mucosa. Gastroenterology 71: 82–86, 1976.
 77. Read, N. W., D. C. Barber, R. J. Levin, and C. D. Holdsworth. Unstirred layer and kinetics of electrogenic absorption in the human jejunum in situ. Gut 18: 865–876, 1977.
 78. Rouse, D. J., and L. Lack. Ion requirements for taurocholate transport by ileal brush border membrane vesicles. Life Sci. 25: 45–52, 1979.
 79. Sallee, V. L. Fatty acid and alcohol partitioning with intestinal brush border and erythrocyte membranes. J. Membr. Biol. 43: 187–201, 1978.
 80. Saunders, D. R., and A. H. Dawson. The absorption of oleic acid in the bile fistula rat. Gut 4: 254–260, 1963.
 81. Schiff, E. R., N. C. Small, and J. M. Dietschy. Characterization of the kinetics of the passive and active transport mechanisms for bile acid absorption in the small intestine and colon of the rat. J. Clin. Invest. 51: 1351–1362, 1972.
 82. Schron, C. M., C. Washington, and B. L. Blitzer. The transmembrane pH gradient drives uphill folate transport in rabbit jejunum. J. Clin. Invest. 76: 2030–2033, 1985.
 83. Schultz, S. G. Salt and water absorption by mammalian small intestine. In: Physiology of the Gastrointestinal Tract, edited by L. R. Johnson New York: Raven, 1981, vol. 2, p. 983–989.
 84. Schultz, S. G., and C. K. Strecker. Cholesterol and bile salt influxes across brush border of rabbit jejunum. Am. J. Physiol. 220: 59–65, 1971.
 85. Schwarz, S. M., B. Hostetler, S. Ling, M. Mone, and J. B. Watkins. Intestinal membrane lipid composition and fluidity during development in the rat. Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G200–G207, 1985.
 86. Schwarz, S. M., S. Ling, B. Hostetter, J. P. Draper, and J. B. Watkins. Lipid composition and membrane fluidity in the small intestine of the developing rabbit. Gastroenterology 86: 1544–1551, 1984.
 87. Schwenk, M., E. Hegazy, and V. Lopez del Pino Kinetics of taurocholate uptake by isolated ileal cells of guinea pig. Eur. J. Biochem. 131: 387–391, 1983.
 88. Schwenk, M., V. Lopez del Pino, and E. Hegazy. Bile acid uptake by isolated intestinal mucosal cells of guinea pig. Biochim. Biophys. Acta 721: 247–252, 1982.
 89. Shiau, Y.‐F., P. Fernandez, M. J. Jackson, and S. McMonagle. Mechanisms maintaining a low‐pH microclimate in the intestine. Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G608–G617, 1985.
 90. Simion, F. A., B. Fleischer, and S. Fleischer. Ionic requirements for taurocholate transport in rat liver plasma membrane vesicles. J. Bioenerg. Biomembr. 16: 507–515, 1984.
 91. Simion, F. A., B. Fleischer, and S. Fleischer. Subcellular distribution of bile acids, bile salts and taurocholate binding sites in rat liver. Biochemistry 23: 6459–6466, 1984.
 92. Simion, F. A., B. Fleischer, and S. Fleischer. Two distinct mechanisms for taurocholate uptake in subcellular fractions from rat liver. J. Biol. Chem. 259: 10814–10822, 1984.
 93. Simmonds, W. J., T. G. Redgrave, and R. L. S. Willix. Absorption of oleic and palmitic acids from emulsions and micellar solutions. J. Clin. Invest. 47: 1015–1025, 1968.
 94. Singh, A., J. A. Balint, R. H. Edmonds, and J. B. Rodgers. Adaptive changes of the rat small intestine in response to a high fat diet. Biochim. Biophys. Acta 260: 708–715, 1972.
 95. Siperstein, M.D., I. Chaikoff, and W. D. Rheinhardt. 14C cholesterol. V. Obligatory function of bile in intestinal absorption of cholesterol. J. Biol. Chem. 198: 111–114, 1952.
 96. Sklan, D. Site of digestion and absorption of lipids and bile acids in the rat and turkey. Comp. Biochem. Physiol. A Comp. Physiol. 65: 91–95, 1980.
 97. Sklan, D., and P. Budowski. The effect of lipids on taurocholate absorption from intestinal loops in the rat. Lipids 12: 193–197, 1977.
 98. Sklan, D., P. Budowski, and S. Hurwitz. Site of bile acid absorption in the rat. Lipids 11: 467–471, 1976.
 99. Smithson, K. W., D. B. Millar, L. R. Jacobs, and G. M. Gray. Intestinal diffusion barrier: unstirred water layer or membrane surface mucous coat? Science Wash. DC 214: 1241–1243, 1981.
 100. Spittell, D., L. K. Vongroven, and M. T. Ravi Subbiah Concentration changes of bile acids in sequential segments of pigeon intestine and their relation to bile acid absorption. Biochim. Biophys. Acta 441: 32–37, 1976.
 101. Stein, W. D. The Movement of Molecules Across Cell Membranes. New York: Academic, 1967, p. 65–85.
 102. Stiehl, A., P. Czygan, W. Frohling, M. Liersch, and B. Kommerell. Sulfation of bile acids. In: Liver and Bile, edited by F. Schaffner, R. Bianchi, W. Gerok, and K. Sickinger. Baltimore, MD: University Park, 1977, p. 129–138.
 103. Thomson, A. B. R. Intestinal absorption of lipids: influence of the unstirred water layer and bile acid micelle. In: Disturbances in Lipid and Lipoprotein Metabolism, edited by J. M. Dietschy, A. M. Gotto, Jr., and J. A. Ontko. Bethesda, MD: Am. Physiol. Soc., 1978, p. 29–55.
 104. Thomson, A. B. R., and L. Cleland. Intestinal cholesterol uptake from phospholipid vesicles and from simple and mixed micelles. Lipids 16: 881–887, 1981.
 105. Thomson, A. B. R., and J. M. Dietschy. Derivation of the equations that describe the effects of unstirred water layers on the kinetic parameters of active transport processes in the intestine. J. Theor. Biol. 64: 277–294, 1977.
 106. Thomson, A. B. R., and J. M. Dietschy. Intestinal lipid absorption: major extracellular and intracellular events. In: Physiology of the Gastrointestinal Tract, edited by L. R. Johnson New York: Raven, 1981, vol. 2, p. 1147–1220.
 107. Thornton, A. G., G. V. Vahouny, and C. R. Treadwell. Absorption of lipids from mixed micellar bile salt solutions. Proc. Soc. Exp. Biol. Med. 127: 629–632, 1968.
 108. Turner, R. J. Stoichiometry of cotransport systems. In: Membrane Transport Driven by Ion Gradients, edited by G. Semenza and R. Kinne. New York: NY Acad. Sci., 1985, p. 10–25.
 109. Von Dippe, P., and D. Levy. Characterization of the bile acid transport system in normal and transformed hepatocytes. J. Biol. Chem. 258: 8896–8901, 1983.
 110. Watt, S. M., and W. J. Simmonds. The specificity of bile salts in the intestinal absorption of micellar cholesterol in the rat. Clin. Exp. Pharmacol. Physiol. 3: 305–322, 1976.
 111. Weinberg, S. L., G. Burckhardt, and F. A. Wilson. Taurocholate transport by rat intestinal basolateral membrane vesicles: evidence for the presence of an anion exchange transport system. J. Clin. Invest. 78: 44–50, 1986.
 112. Weiner, I. M., and L. Lack. Absorption of bile salts from the small intestine in vivo. Am. J. Physiol. 202: 155–157, 1962.
 113. Westergaard, H., and J. M. Dietschy. Delineation of the dimensions and permeability characteristics of the two major diffusion barriers to passive mucosal uptake in the rabbit intestine. J. Clin. Invest. 54: 718–732, 1974.
 114. Westergaard, H., and J. M. Dietschy. The mechanism whereby bile acid micelles increase the rate of fatty acid and cholesterol uptake into the intestinal mucosal cell. J. Clin. Invest. 58: 97–108, 1976.
 115. Wieland, T., M. Nassal, W. Kramer, G. Fricker, U. Bickel, and G. Kurz. Identity of hepatic membrane transport systems for bile salts, phalloidin, and antamanide by photoaffinity labeling. Proc. Natl. Acad. Sci. USA 81: 5232–5236, 1984.
 116. Wilson, F. A. Intestinal transport of bile acids. Am. J. Physiol. 241 (Gastrointest. Liver Physiol. 4): G83–G92, 1981.
 117. Wilson, F. A. Intestinal plasma membrane vesicles and bile acid transport. In: Enterohepatic Circulation of Bile Acids and Sterol Metabolism, edited by G. Paumgartner, A. Stiehl, and W. Gerok. Hingham, MA: MTP, 1985, p. 103–108.
 118. Wilson, F. A., G. Burckhardt, H. Murer, G. Rumrich, and K. J. Ullrich. Sodium‐coupled taurocholate transport in the proximal tubule of the rat kidney in vivo and in vitro. J. Clin. Invest. 67: 1141–1150, 1981.
 119. Wilson, F. A., and J. M. Dietschy. Approach to the malabsorption syndromes associated with disordered bile acid metabolism. Arch. Intern. Med. 130: 584–594, 1972.
 120. Wilson, F. A., and J. M. Dietschy. Characterization of bile acid absorption across the unstirred water layer and brush border of the rat jejunum. J. Clin. Invest. 51: 3015–3025, 1972.
 121. Wilson, F. A., and J. M. Dietschy. The intestinal unstirred layer: its surface area and effect on active transport kinetics. Biochim. Biophys. Acta 363: 112–126, 1974.
 122. Wilson, F. A., V. L. Sallee, and J. M. Dietschy. Unstirred water layers in intestine: rate determinant of fatty acid absorption from micellar solutions. Science Wash. DC 174: 1031–1033, 1971.
 123. Wilson, F. A., and L. L. Treanor. Characterization of the passive and active transport mechanisms for bile acid uptake into rat isolated intestinal epithelial cells. Biochim. Biophys. Acta 406: 280–293, 1975.
 124. Wilson, F. A., and L. L. Treanor. Glycodeoxycholate transport in brush border membrane vesicles isolated from rat jejunum and ileum. Biochim. Biophys. Acta 554: 430–440, 1979.
 125. Wilson, F. A., and L. L. Treanor. Studies of relationships among bile acid uptake, Na+K+‐ATPase, and Na+ gradient in isolated cells from rat ileum. Gastroenterology 81: 54–60, 1981.
 126. Wingate, D. L., S. F. Phillips, and A. F. Hofmann. Effect of glycine‐conjugated bile acids with and without lecithin on water and glucose absorption in perfused human jejunum. J. Clin. Invest. 52: 1230–1236, 1973.
 127. Winne, D. Unstirred layer thickness in perfused rat jejunum in vivo. Experientia 32: 1278–1279, 1976.
 128. Winne, D. Shift of pH‐absorption curves. J. Pharmacokinet. Biopharm. 5: 53–94, 1977.

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Frederick A. Wilson. Intestinal Transport of Bile Acids. Compr Physiol 2011, Supplement 19: Handbook of Physiology, The Gastrointestinal System, Intestinal Absorption and Secretion: 389-404. First published in print 1991. doi: 10.1002/cphy.cp060416