Open AccessCobalt Induction of Hepatic Heme Oxygenase; with Evidence That Cytochrome P -450 Is Not Essential for This Enzyme Activity
Author(s) -
Mahin D. Maines,
Attallah Kappas
Publication year - 1974
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.71.11.4293
Subject(s) - heme , microsome , cytochrome , chemistry , biochemistry , heme oxygenase , cytochrome p450 reductase , hemeprotein , reductase , enzyme , cytochrome p450 , cytochrome c , coenzyme q – cytochrome c reductase , mitochondrion
Treatment of ratsin 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 cytochromeP -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 cytochromeP -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 cytochromeP -450 content was decreased to spectrally unmeasurable amounts after incubation with 4 M urea. The same treatment eliminated ehtylmorphine demethylation and decreased microsomal NADPH-cytochromec 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 ) cytochromeP -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-cytochromec 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.