Flock, Eunice V.

Abstract Rapid formation of C14-bilirubin from glycine-2-C14 or δ-aminolevulinic acid-4-C14 has been demonstrated in isolated, perfused rat liver. The kinetics of labeled bilirubin production in vitro were similar to those of the "early labeling" pigment fraction observed in intact rats. The magnitude of bile pigment formation from C14-ALA by isolated liver was comparable to that in intact animals. Derivation of the C14-bilirubin from hepatic degradation of labeled hemoglobin was excluded by perfusion of the liver with blood poor in reticulocytes, or with plasma. The findings identify the liver as an important source of the "early-labeling" pigment fraction.

The isolated, perfused rat liver has been used to study the metabolic pathways of I131-labeled l-thyroxine (T4), l-3,5,3'-triiodothyronine (T3), their partially deiodinated derivatives, and d-thyroxine. l-Thyroxine was metabolized less rapidly than the l-thyronines with fewer iodine atoms. l-T4 accumulated in the liver more rapidly than l-3,3',5'T3 or l-3,3'T2 but less rapidly than l-3,5,3'T3 or d-T4. Conjugation with glucuronic acid proceeded in the liver most rapidly from 3,5,3'T3 and at much lower rates from d-T4, l-T4, l-3,3',5'T3, and l-3,3'-diiodothyronine (T2). Deiodination of l-3,3',5'T3 and l-3,3'T2 proceeded most rapidly.

Dogs with biliary fistulas metabolized triiodothyronine rapidly to inorganic iodide, as did normal dogs. The amount and distribution of I131 compounds in the urine were not greatly altered by withdrawal of the bile, which contained about one-fourth of the I131 administered. Dogs with biliary obstruction excreted more of compounds b, iodide and the conjugate than normal dogs. The absence of enterohepatic circulation of metabolic products of triiodothyronine usually excreted in the bile did not appreciably alter the products or rate of metabolism of triiodothyronine. Some of the same products of triiodothyronine appeared in both bile and urine but there was very little inorganic iodide in the bile and much more of the glucuronide and the water-soluble, column residual fraction.

The total amount of I131-containing compounds excreted in the urine of the dehepatized dog receiving either radioactive thyroxine or triiodothyronine is similar to that of the normal dog receiving similar injections. The important role of the liver in the deiodination of thyroxine and triiodothyronine is indicated by the failure of the liverless animal to convert these compounds to inorganic iodide as completely as does the normal dog. Only a small percentage of the I131 compounds excreted by the liverless dog appears as inorganic iodide. The most abundant iodine compound in the urine of the dehepatized dog is a conjugate of thyroxine when thyroxine is injected, and an unidentified compound, b, when triiodothyronine is injected.