PMID: 41795Aug 1, 1979

Reduction of anthracycline glycoside by NADPH--cytochrome P-450 reductase

Gann = Gan
T KomiyamaH Umezawa

Abstract

The in vitro degradation of the new antitumor anthracycline antibiotic, aclacinomycin-A, was studied using rat liver homogenate. In the presence of NADH or NADPH, the glycosidic bond at C-7 position of aclacinomycin-A was reductively cleaved to produce 7-deoxyaklavinone and 7-deoxyaklavinone dimer, MA144 E1. Subcellular fractionation indicated that most of the enzyme activity was present in the microsomal fraction and required anaerobic condition and NADPH. The purified enzyme reduced the glycosidic metabolites, MA144 M1 and MA144 N1, as well as aclacinomycin-A. The optimum pH for the anthracycline glycoside reductase reaction using aclacinomycin-A as substrate was 7.4. The enzyme was sigmoidally saturated with aclacinomycin-A and showed the concentration of 1.2 x 10(-4) M required for half maximal activity, and Km value of 7.7 x 10(-5) M for NADPH. The degradative pathway of aclacinomycin-A and its glycosidic metabolites was discussed.

Related Concepts

Biochemical Pathway
NADPH-Ferrihemoprotein Reductase
Aclarubicin
NADH
Cardiac Glycosides
Aclarubicin hydrochloride
Subcellular Fractionation
Microsomes, Liver
Cleaved Cell
Enzyme Activity

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