FORMATION OF BETA-GLUCURONIDES AND OF BETA-GALACTURONIDES OF VARIOUS RETINOIDS CATALYZED BY INDUCED AND NONINDUCED MICROSOMAL UDP-GLUCURONOSYLTRANSFERASES OF RAT-LIVER

The complex of microsomal UDP-glucuronosyl transferases (UGT; EC 2.4.1 .17) of rat liver catalyzes the formation of retinoyl beta-glucuronide (RAG) from retinoic acid (RA) and retinyl beta-glucuronide (ROG) from retinol (ROL) in the presence of UDP-glucuronic acid (UDPGA). The rel ative rates of formation of beta-glucuronides in noninduced microsomes were: 9-cis RA > 13-cis RA > all-trans 4-oxo RA > TTNPB > all-trans R A > CD-367 > 13-cis ROL > 9-cis ROL > acitretin > all-trans ROL. Micha elis constants (K-M) for all-trans RA, 13-cis ROL, TTNPB and UDPGA wer e 130 mu M, 300 mu M, 210 mu M and 2.6 mM, respectively. Galacturonide s of RA, but not detectably of ROL, were formed from UDP-galacturonic acid at 11-30% the rate of the beta-glucuronides, whereas UDP derivati ves of nonionized sugars did not serve as substrates. Pretreatment of rats with 3-methylcholanthrene markedly increased RAG formation in the absence of detergent (Triton X-100), but less so in its presence. Clo fibrate pretreatment doubled the rate of RAG formation, whereas phenob arbital pretreatment showed little effect. N-Ethylmaleimide (5 mM) min imized cis-trans isomerization without significantly affecting glucuro nidation. Rates of glucuronidation of retinoids clearly depend both on their isomeric states and on their chemical structures. Different UGT enzymes might well act on different geometric isomers of RA.