Microsomal reductive glycosidase

Abstract

Rat liver microsomes contain a phenobarbital inducible, NADPH dependent, reductive glycosidase capable of cleaving several anthracycline antibiotics, including adriamycin and daunorubicin, to deoxyaglycone products. The pH optimum for the reaction ranges from 7 to 7.4, and no metal requirements are noted. Molecular oxygen reversibly inhibits the microsomal enzyme greater than 95% at 20% oxygen partial pressure. Carbon monoxide, SKF 525A and sulfhydryl reagents are not inhibitory to the reaction, but the enzyme is sensitive to Cu++ and Zn++. Since the intact glycoside is necessary for conversion to the deoxyaglycone and a possible intermediate hydroxylated aglycone is not reduced to the deoxyaglycone, a concerted reaction mechanism is proposed. The reductive glycosidase activity is also present in rat brain, kidney and other tissues. Sensitivity of this enzyme to molecular oxygen suggests a possible regulatory role for the enzyme in vivo.