Hepatic heme metabolism: possible role of biliverdin in the regulation of heme oxygenase activity.
Treatment of rats with biliverdin (48 h) resulted in an increase in microsomal heme oxygenase activity in the liver. This was accompanied by decreases in the microsomal heme and cytochrome P-450 contents. In these respects cellular responses elicited by biliverdin resembled those produced by hematin (48 h). When rats were treated with biliverdin for a short interval (3 h) an inhibition of the activities of heme oxygenase and biliverdin reductase, concomitant with an increase in microsomal heme and cytochrome P-450 contents, were observed. Hematin was ineffective in altering these parameters under similar conditions. Biliverdin, in a concentration-dependent manner, inhibited the activities of purified heme oxygenase and biliverdin reductase. The activity of purified rat liver heme oxygenase was refractory to bilirubin, whereas that of purified biliverdin reductase was severely inhibited. It is suggested that biliverdin regulates cellular heme degradation processes by occupying the heme binding site on heme oxygenase, thus hindering the access of the substrate to the catalytic site of the enzyme.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D001663:Bilirubin / Q000031:analogs & derivatives*; D001664:Biliverdine / Q000502:physiology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006427:Hemin / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D051381:Rats; D011919:Rats, Inbred Strains
D065607:Cytochrome P-450 Enzyme Inhibitors; D006418:Heme; D006427:Hemin; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D006419:Heme Oxygenase (Decyclizing); D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase; D000624:5-Aminolevulinate Synthetase; D001664:Biliverdine; D001663:Bilirubin