Microsomal reductive glycosidase.
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.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology; D003630:Daunorubicin / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000648:ultrastructure; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010100:Oxygen / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D013439:Sulfhydryl Reagents; D002248:Carbon Monoxide; D011335:Proadifen; D006026:Glycoside Hydrolases; D010100:Oxygen; D003630:Daunorubicin