期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1974
卷号：71
期号：11
页码：4293-4297
DOI：10.1073/pnas.71.11.4293
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Treatment of rats in vivo with cobalt chloride stimulated heme oxidation by hepatic microsomes to levels up to 800% above controls. This treatment also caused increases in liver weight and in total microsomal protein; in contrast, marked decreases were produced in microsomal oxidation of ethylmorphine (80%), and in cytochrome P-450 (60-70%) and heme (30-50%) contents. Cobalt chloride treatment did not affect heme oxidation by the spleen heme oxygenase system. The rate of heme oxidation by hepatic microsomal enzymes and the microsomal content of cytochrome P-450 were found to be unrelated. This conclusion was reached from studies in which microsomal heme oxygenase activity from cobalt-treated animals could be increased by 900% above control levels in the same microsomal preparation in which cytochrome P-450 content was decreased to spectrally unmeasurable amounts after incubation with 4 M urea. The same treatment eliminated ehtylmorphine demethylation and decreased microsomal NADPH-cytochrome c reductase (EC 1.6.2.4 ) activity by 75%. It is concluded that (i) the hepatic microsomal enzyme system that oxidizes heme compounds is not the same as that which metabolizes drugs, (ii) cytochrome P-450 is not essential for the oxidation of heme by liver cells, (iii) there is no direct relationship between the rate of heme oxidation and the level of NADPH-cytochrome c reductase activity, and (iv) the oxidation of heme is protein-dependent and the active proteins are inducible, but are different from those involved in drug metabolism.
