The effects of pH on the enzymatic formation of beta-glucuronides of various retinoids by induced and noninduced, microsomal UDPGA-glucuronosyltransferases of several rat tissues in vitro

All-trans retinoyl-beta-glucuronide, a prominent water-soluble metabolite o f all-trans retinoic acid (RA) in animals, is formed by the enzymic transfe r of the glucuronyl moiety of uridine diphosphoglucuronic acid to RA. Uridi ne diphosphoglucuronic acid glucuronosyl transferases (UGTs) of microsomal preparations catalyze this reaction. In noninduced rat liver microsomes, ma ximal activity was observed in the physiologic range (pH 6.9-7.5)for all-tr ans-RA, 9-cis-RA, all-trans-4-oxo-RA, and the synthetic retinoid tetramethy l, tetrahydro-anthracenyl-benzoic acid. The activities toward 13-cis-RA and tetramethyl, tetrahydronaphthenyl-propenyl-benzoic acid were maximal betwe en pH 5.4 and 6.9 and toward acitretin [9-(2',3'.6' trimethyl, 4'methoxyben zyl-1') 3,7 dimethyl, nona-2,4,6,8 tetraenoic acid] at pH 8,4. Several orga ns catalyze this reaction, but the activities of noninduced microsomes from liver, kidney, and testes were higher than those from intestine and lung. Brain microsomes were inactive. During storage at -80 degrees C, the srabil ity of UGTs varied both with the tissue and the retinoid substrate. 3-Methy lcholanthrene both induces UGTs and increases the permeability of microsoma l preparations to its substrates. The rates of glucuronidation of the less biologically active retinoids all-trans-4-oxo RA and 13-cis-RA were increas ed relatively more (11-fold and 6-fold, respectively) than those of the nat ural ligands far nuclear transcription factors all-trans-RA and 9-cis-RA (t hreefold and twofold, respectively). We conclude that several microsomal UG Ts, which are differentially regulated, act an retinoids. (J. Nutr. Biochem . 9:676-681, 1998) (C) Elsevier Science Inc. 1998.