Journal of Lipid Research, Vol. 7, 3-9, January 1966
Copyright © 1966 by Lipid Research, Inc.

Formation and enterohepatic circulation of metabolites of retinol and retinoic acid in bile duct-cannulated rats

R. D. Zachman , P. E. Dunagin Jr. , and J. A. Olson

Department of Biochemistry, College of Medicine, University of Florida, Gainesville, Florida

Four hours after intraportal injection of retinoic acid-¹⁴C into bile duct-cannulated rats, less than 10% of the radioactivity was recovered in the liver, intestine, and kidneys. Within 6 hr, 40% of the radioactivity had appeared in bile. When suspensions of retinol-¹⁴C or retinal were similarly injected, 25-35% of the dose was excreted in bile within 24 hr and equivalent amounts were deposited in the liver as retinol ester. The isolated perfused liver also produced these bile metabolites and is probably the major site of their formation in vivo. The intestine may metabolize retinoic acid, however, since some metabolites were found in the intestinal wall and lumen, even in bile duct-cannulated rats.

The bile metabolites of retinol-¹⁴C and retinoic acid-¹⁴C undergo extensive enterohepatic circulation. The bile radioactivity was not volatilized on boiling at acid pH, was not present in digitonin-precipitated sterols, and did not migrate with bile salts on reversed-phase paper chromatography. Anion-exchange chromatography resolved the metabolites of bile into three fractions containing nonionic compounds, acidic substances like retinoic acid, and more polar acidic derivatives.

Supplementary key words retinal-¹⁴C • preparation • retinoic acid • retinol • retinal • metabolism • rat • metabolites • liver • intestine • bile • enterohepatic circulation • anion-exchange chromatography • excretion

Submitted on June 9, 1965
Accepted on August 10, 1965

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