Marmoset flavin-containing monooxygenase 3 in liver is a major benzydamine and sulindac sulfide oxygenase.

Uehara S, Shimizu M, Uno Y et al.

Showa Pharmaceutical University.

Drug metabolism and disposition: the biological fate of chemicals. Mar 2017.

Common marmosets (Callithrix jacchus) are potentially primate models for preclinical drug metabolism studies because the molecular characteristics of cytochrome P450 (P450) enzymes have similarities between this species and humans. However, characterization of non-P450 enzymes have not been clarified in marmosets. Here, we report characterization of flavin-containing monooxygenase (FMO) 1-5 identified in marmoset tissues. Marmoset FMO forms shared high amino acid sequence identities (93-95%) and phylogenetic closeness with human homologue FMO forms. FMO1 and FMO3 mRNA were abundantly expressed in livers and kidneys among five marmoset tissues examined, where FMO3 protein were detected by immunoblotting. FMO inhibition assays using preheated tissue microsomes indicated that benzydamine N-oxygenation and sulindac sulfide S-oxygenation in marmoset livers was mainly catalyzed by FMO3, the major hepatic FMO. Marmoset FMO3 protein heterologously expressed in Escherichia coli effectively catalyzed benzydamine N-oxygenation and sulindac sulfide S-oxygenation comparable to marmoset liver microsomes. These results indicated that FMO3 enzyme expressed in marmoset livers mainly metabolized benzydamine and sulindac sulfide, typical human FMO substrates, suggesting its importance for FMO-dependent drug metabolism in marmosets.

Pubmed

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