Cutaneous β-glucuronidase: cleavage of mycophenolic acid by preparations of mouse skin.

Mycophenolic acid, a new chemotherapeutic agent for the treatment of psoriasis, is known to be rapidly conjugated on absorption and to circulate largely in the form of its glucuronide conjugate. Since this metabolite does not readily penetrate intact cells and is cleaved by the enzyme β-glucuronidase to yield free mycophenolic acid, the ability of preparations of mouse skin to cleave mycophenolic glucuronide was studied. The time course of mycophenolic acid liberation by such preparations and the dependence upon the amount of enzyme preparation were demonstrated. Preparations of mouse skin and mouse liver, kidney, spleen, lung, heart and small intestine were assayed for β-glucuronidase activity using p-nitrophenyl-β-D-glucuronide as substrate. Skin yielded preparations with higher β-glucuronidase activity per/mg protein than any of the other organs tested. When expressed on the basis of β-glucuronidase activity recovered per milligram of tissue DNA, skin, liver and kidney showed higher levels than the other organs tested. [ABSTRACT FROM AUTHOR]