Bile acid inhibition of taurocholate uptake by rat hepatocytes: role of OH groups
To define further the structural specificity of the taurocholate uptake site, the authors studied the ability of a variety of taurine-conjugated bile acids with differing hydroxyl substituents on the sterol moiety to inhibit (/sup 14/C) taurocholate uptake. Rat hepatocytes isolated by collagenase perfusion were incubated in a tris (hydroxymethyl) aminomethane-phosphate buffer containing (/sup 14/C)taurocholate in the presence or absence of inhibitor bile acid. Stronger inhibitors were studied at a fixed concentration of 5 ..mu..M, weaker ones at 25 ..mu..M. Initial uptake velocity was measured. Uptake velocity could then be related to taurocholate concentration and a V/sub max/ and K/sub m/ could be determined by applying a nonlinear least squares fit to the data obtained with or without inhibitor. The kinetic parameters allowed the determination of the type of inhibition and of inhibition constants (K/sub i/) of the various test bile acids. The data indicate that bile acids containing a 6- or 7-OH group exhibit competitive inhibition, whereas bile acids with no 6- or 7-OH group exhibit noncompetitive inhibition. Of the compounds exhibiting competitive inhibition, K/sub i/ varied with the number of hydroxyl groups on the sterol moiety. They conclude that the presence of absence of a 6- or 7-OH group dictates the mechanism of inhibition; the number of hydroxyl substituents determines the potency of competitive inhibition.
- Research Organization:
- Univ. of Modena, Italy
- OSTI ID:
- 5445346
- Journal Information:
- Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 252:3; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMAL CELLS
ANIMALS
BILE ACIDS
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMISTRY
CHOLIC ACID
HORMONES
HYDROGEN COMPOUNDS
HYDROXIDES
HYDROXY COMPOUNDS
INHIBITION
INSULIN
KINETICS
LABELLED COMPOUNDS
LIVER CELLS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDE HORMONES
RATS
REACTION KINETICS
RODENTS
SOMATIC CELLS
STEROIDS
STEROLS
SULFONIC ACIDS
TAURINE
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES